CME ONLINE: Limited Resource Setting Management of Outpatient Diabetes

CME ONLINE: Limited Resource Setting Management of Outpatient Diabetes

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nitial Outpatient Management of Type 2 Diabetes in Haiti

This case was created by:

James Hudspeth, MD
Department of General Internal Medicine
Boston University School of MedicineAnand Vaidya, MD
Instructor in Medicine
Department of Endocrinology, Diabetes & Hypertension
Brigham and Women’s Hospital

Zadok Sacks, MD
Clinical Instructor in Medicine
Medicine-Brigham and Women’s Hospital
Brigham and Women’s Hospital

Initial Outpatient Management of Type 2 Diabetes in Haiti

Pretest

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Case Presentation

A 56-year-old woman, Mrs. S., comes to see you at your clinic in rural Haiti. She complains of having experienced fatigue for several months, increasing over the last few weeks.

History

On further questioning, she notes mild polyuria and polydipsia, as well as occasional blurry vision, going on for several months. She denies pedal edema, shortness of breath, or orthopnea. She denies dysuria or hematuria. She denies weight loss in the last several months. All other questions are negative.

She works as a seamstress in a nearby village. Her husband is deceased, and she has several adult children. She has a small house and has a mobile phone, but does not have electricity in her house. She almost always has enough to eat, and denies having to skip meals, but does not have a lot of money.

Findings

Her physical exam is notable for obesity (BMI of 32), a blood pressure of 156/80, and intact sensation to vibration and light touch in her feet. She does not have conjuctival pallor, S3 or S4 on cardiac exam, signs of dehydration, or lower extremity edema. Her pulses are 2+ at her doralis pedis and posterior tibialis. You note acanthosis nigricans on her neck. All other exam findings are negative.

A urine dipstick shows 0+ protein, 0+ ketones, and 3+ glucose; her non-fasting blood glucose is 180 mg/dL. A basic metabolic panel does not demonstrate renal failure (her creatinine is 0.9 and her BUN is 9) or acidosis.

You make a tentative diagnosis of chronic hyperglycemia due to type 2 diabetes. A fasting glucose test done the next day confirms the diagnosis (140 mg/dL, higher than the WHO criteria for diagnosis of equal to or great than 126 mg/dL; with her symptoms, a random blood glucose of equal to or greater than 200 mg/dL would also have been diagnostic) (1,2).

Question 1 of 4

What is the most reasonable initial management of your patient’s diabetes, within the Haitian context?

		a.	Insulin on a weight-based regimen along with counseling on diet and exercise The authors disagree.The International Diabetes Federation and American Diabetes Association guidelines (1,2) both recommend the initiation of insulin when maximal oral agents have failed to provide adequate glycemic control, or sooner as clinically indicated (for example, a patient with an hemoglobin HbA_1c of 11% would be very unlikely to obtain adequate glycemic control with diet, exercise, and oral agents only). For this Haitian patient, while insulin initiation is not contraindicated, it raises substantially more challenges than oral medication for both the physician as well as for the patient. Insulin requires at least daily (often more frequent) injections with sterile needles, daily blood glucose testing, intensive education on the proper use of insulin and the warning signs of hypoglycemia, as well as a reliably cool (ideally refrigerated) location for insulin storage. This patient has limited financial resources, and lacks a refrigerator in particular.While insulin is very effective, due to the difficulties and costs in implementing its use in Haiti, it is worth trying oral medications first (which can also be very effective), along with diet and exercise counseling (which applies to all diabetic patients). The point at which to start insulin will vary depending on the resources available at your clinic and the resources of the patient in question. For Mrs. S., while she may eventually require insulin, initially she may do well with oral agents alone. Because she demonstrates no signs of pronounced hypovolemia, acidosis or renal impairment, she is not in any immediate danger of hyperosmotic sequelae, which would necessitate at least temporary insulin use and possibly hospitalization.
		b.	Metformin twice a day along with counseling on diet and exercise The answer is correct.Mrs. S. will need a thorough discussion about diabetes, how it is treated, and why it is important to continue with these therapies even once she feels better. If her glucose was very elevated (to the >300 range) and she had signs of hypovolemia, or if she had acidosis with or without renal impairments on her labs, treatment with insulin and intravenous fluids to rapidly correct her blood glucose and prevent complications would be indicated. Mrs. S. does not appear to be dehydrated on exam, so she may be told to increase her intake of non-sugary fluids for a few days, and started on metformin. She should also be advised on increasing her exercise (for example, walking for an hour every evening), and on specifics of an appropriate diet (see answer C for more information on diet).The use of oral medications to lower blood glucose has been shown in a number of trials to reduce the risk of diabetic complications; it may also reduce the risk of death in some populations, though this effect has not been demonstrated as thoroughly (1). In general, metformin is presently the preferred starting medication for most (BMI of 25 or greater) patients with type 2 diabetes (1,2) who do not require insulin. When compared to other medications in trials, metformin is associated with essentially no hypoglycemia, less weight gain (often weight loss, in fact), and potentially a greater reduction in the risk for complications of diabetes. Due to a rare risk of lactic acidosis, it should be used cautiously in patients with impaired kidney function (estimate glomerular filtration rate of equal to or less than 45 ml/min/1.73 m²) (1). It often causes diarrhea, abdominal cramping, and nausea/vomiting. These symptoms usually wane with time, and can be reduced by starting with a low dose (500mg once or twice a day, taken with food) and increasing the dose over several weeks (maximum of 2500 mg/day, split into two to three doses). Mrs. S. should be warned about these adverse effects and the importance of taking the medicines should be emphasized. The glycemic control goal, depending on the guidelines used, is to aim for a HbA_1c of 7% or less (1, 2), or a fasting plasma glucose of <115 mg/dL (1) or 70-130 mg/dL (2), or a plasma glucose two hours after a meal of <160 mg/dL (1) or <180 mg/dL (2). In a low-resource setting such as Haiti, where more intensive monitoring is not possible, where the dangers of hypoglycemia are higher, and where the long-term benefits of ultra-aggressive glycemic control are unclear, a HbA_1c goal of 7% is a reasonable target; Table 1 shows the correlation between HbA1c and the average sugar through the day. If HbA_1c cannot be measured, a fasting plasma glucose can be substituted as a crude alternative (in which case the goal of a fasting plasma glucose <130 (mg/dL) would be the target); note that HbA_1c is the preferred lab test to monitor long-term glycemic control whenever possible, and that fasting plasma glucose values can be skewed by prior meals, exercise, and infection. Because it is a long-term measure, HbA_1c when avaiable should only be checked every three months (2). Should Mrs. S. ever have low sugars or if there are difficulties in monitoring her sugars, more relaxed goals are reasonable to set, particularly when using agents that can cause hypoglycemia. If she cannot reach her glycemic target after a maximal dose of metformin for several months, a sulfonylurea can be added to her regimen. Table 1. Estimated average blood glucose based on hemoglobin A_1c percent. Adapted from The American Diabetes Association.
		c.	Advice on a diabetic diet and encouraging exercise alone The authors disagree.This is an important part of managing any patient with diabetes. All clinics and hospitals should have staff who can discuss the importance with patients of managing their diet to reduce simple carbohydrates (white rice, beans, sugar, sodas, juices, fruits, white potatoes, plantains) and increase the amount of complex carbohydrates, vegetables, and proteins. Similarly, patients who do not have an active lifestyle should be encouraged to engage in exercise (such as walking for 30 minutes every day).Unfortunately, given how high her glucose is, diet and exercise alone are very unlikely to reduce her rangesblood sugars adequately. Moreover, the ADA guidelines (2) recommend that any patient diagnosed with diabetes be started on a medical therapy, typically metformin or, if very poorly controlled, insulin (see other answers for further discussion).
		d.	Glipizide or another sulfonylurea, once a day before her largest meal, along with counseling on diet and exercise The authors disagree.Metformin is the oral agent of choice for most patients, though a sulfonylurea can be used as an alternative if clinically indicated, or if metformin is unavailable (1,2). Glibenclamide is the WHO-recommended sulfonylurea. These agents have a real risk of hypoglycemia (unlike metformin), and should be used with caution in patients with impaired function of the kidneys or liver, as these increase the risk of hypoglycemia. Dosing depends on the sulfonylurea being used, but would typically start with once a day before the largest meal of the day.

Case Presentation

A 56-year-old woman, Mrs. S., comes to see you at your clinic in rural Haiti. She complains of having experienced fatigue for several months, increasing over the last few weeks.

History

On further questioning, she notes mild polyuria and polydipsia, as well as occasional blurry vision, going on for several months. She denies pedal edema, shortness of breath, or orthopnea. She denies dysuria or hematuria. She denies weight loss in the last several months. All other questions are negative.

Her physical exam is notable for obesity (BMI of 32), a blood pressure of 156/80, and intact sensation to vibration and light touch in her feet. She does not have conjuctival pallor, S3 or S4 on cardiac exam, signs of dehydration, or lower extremity edema. Her pulses are 2+ at her doralis pedis and posterior tibialis. You note acanthosis nigricans on her neck. All other exam findings are negative.

Question 1 of 4

What is the most reasonable initial management of your patient’s diabetes, within the Haitian context?

CORRECT!
Please read below for feedback for all answer choices
and to compare your answers with your peers.

Correct Choices:

Metformin twice a day along with counseling on diet and exercise

The answer is correct.Mrs. S. will need a thorough discussion about diabetes, how it is treated, and why it is important to continue with these therapies even once she feels better. If her glucose was very elevated (to the >300 range) and she had signs of hypovolemia, or if she had acidosis with or without renal impairments on her labs, treatment with insulin and intravenous fluids to rapidly correct her blood glucose and prevent complications would be indicated. Mrs. S. does not appear to be dehydrated on exam, so she may be told to increase her intake of non-sugary fluids for a few days, and started on metformin. She should also be advised on increasing her exercise (for example, walking for an hour every evening), and on specifics of an appropriate diet (see answer C for more information on diet).

The use of oral medications to lower blood glucose has been shown in a number of trials to reduce the risk of diabetic complications; it may also reduce the risk of death in some populations, though this effect has not been demonstrated as thoroughly (1).

In general, metformin is presently the preferred starting medication for most (BMI of 25 or greater) patients with type 2 diabetes (1,2) who do not require insulin. When compared to other medications in trials, metformin is associated with essentially no hypoglycemia, less weight gain (often weight loss, in fact), and potentially a greater reduction in the risk for complications of diabetes. Due to a rare risk of lactic acidosis, it should be used cautiously in patients with impaired kidney function (estimate glomerular filtration rate of equal to or less than 45 ml/min/1.73 m²) (1).

It often causes diarrhea, abdominal cramping, and nausea/vomiting. These symptoms usually wane with time, and can be reduced by starting with a low dose (500mg once or twice a day, taken with food) and increasing the dose over several weeks (maximum of 2500 mg/day, split into two to three doses). Mrs. S. should be warned about these adverse effects and the importance of taking the medicines should be emphasized.

The glycemic control goal, depending on the guidelines used, is to aim for a HbA_1c of 7% or less (1, 2), or a fasting plasma glucose of <115 mg/dL (1) or 70-130 mg/dL (2), or a plasma glucose two hours after a meal of <160 mg/dL (1) or <180 mg/dL (2).

In a low-resource setting such as Haiti, where more intensive monitoring is not possible, where the dangers of hypoglycemia are higher, and where the long-term benefits of ultra-aggressive glycemic control are unclear, a HbA_1c goal of 7% is a reasonable target; Table 1 shows the correlation between HbA1c and the average sugar through the day. If HbA_1c cannot be measured, a fasting plasma glucose can be substituted as a crude alternative (in which case the goal of a fasting plasma glucose <130 (mg/dL) would be the target); note that HbA_1c is the preferred lab test to monitor long-term glycemic control whenever possible, and that fasting plasma glucose values can be skewed by prior meals, exercise, and infection. Because it is a long-term measure, HbA_1c when avaiable should only be checked every three months (2).

Should Mrs. S. ever have low sugars or if there are difficulties in monitoring her sugars, more relaxed goals are reasonable to set, particularly when using agents that can cause hypoglycemia. If she cannot reach her glycemic target after a maximal dose of metformin for several months, a sulfonylurea can be added to her regimen.

Table 1. Estimated average blood glucose based on hemoglobin A_1c percent.
Adapted from The American Diabetes Association.

Incorrect Choices:

Insulin on a weight-based regimen along with counseling on diet and exercise

The authors disagree.The International Diabetes Federation and American Diabetes Association guidelines (1,2) both recommend the initiation of insulin when maximal oral agents have failed to provide adequate glycemic control, or sooner as clinically indicated (for example, a patient with an hemoglobin HbA_1c of 11% would be very unlikely to obtain adequate glycemic control with diet, exercise, and oral agents only). For this Haitian patient, while insulin initiation is not contraindicated, it raises substantially more challenges than oral medication for both the physician as well as for the patient. Insulin requires at least daily (often more frequent) injections with sterile needles, daily blood glucose testing, intensive education on the proper use of insulin and the warning signs of hypoglycemia, as well as a reliably cool (ideally refrigerated) location for insulin storage. This patient has limited financial resources, and lacks a refrigerator in particular.

While insulin is very effective, due to the difficulties and costs in implementing its use in Haiti, it is worth trying oral medications first (which can also be very effective), along with diet and exercise counseling (which applies to all diabetic patients). The point at which to start insulin will vary depending on the resources available at your clinic and the resources of the patient in question.

For Mrs. S., while she may eventually require insulin, initially she may do well with oral agents alone. Because she demonstrates no signs of pronounced hypovolemia, acidosis or renal impairment, she is not in any immediate danger of hyperosmotic sequelae, which would necessitate at least temporary insulin use and possibly hospitalization.

Advice on a diabetic diet and encouraging exercise alone

The authors disagree.This is an important part of managing any patient with diabetes. All clinics and hospitals should have staff who can discuss the importance with patients of managing their diet to reduce simple carbohydrates (white rice, beans, sugar, sodas, juices, fruits, white potatoes, plantains) and increase the amount of complex carbohydrates, vegetables, and proteins. Similarly, patients who do not have an active lifestyle should be encouraged to engage in exercise (such as walking for 30 minutes every day).

Unfortunately, given how high her glucose is, diet and exercise alone are very unlikely to reduce her rangesblood sugars adequately. Moreover, the ADA guidelines (2) recommend that any patient diagnosed with diabetes be started on a medical therapy, typically metformin or, if very poorly controlled, insulin (see other answers for further discussion).

Glipizide or another sulfonylurea, once a day before her largest meal, along with counseling on diet and exercise

The authors disagree.Metformin is the oral agent of choice for most patients, though a sulfonylurea can be used as an alternative if clinically indicated, or if metformin is unavailable (1,2). Glibenclamide is the WHO-recommended sulfonylurea. These agents have a real risk of hypoglycemia (unlike metformin), and should be used with caution in patients with impaired function of the kidneys or liver, as these increase the risk of hypoglycemia. Dosing depends on the sulfonylurea being used, but would typically start with once a day before the largest meal of the day.

Compare Your Answer

Question 2 of 4

What complications of diabetes should you screen for?

Correct Choices:

Kidney disease, neuropathy, and retinopathy

The answer is correct.The complications of diabetes are divided into microvascular and macrovascular in nature. Microvascular disease affects a number of organs, notably the kidneys, the eyes, and the nervous system. Since all of these complications are typically asymptomatic at first, all newly diagnosed diabetics should have all of the screening tests recommended below.

Kidney disease should be screened for with a serum creatinine as well as a urine testing looking for protein (ideally a test specific for microalbuminuria, which is much more sensitive than a generic urine dipstick) – if protein is found on urine testing, urinary tract infection should be ruled out and the test repeated, ideally with urinary albumin/creatinine or urinary protein/creatinine testing. If proteinuria is confirmed on two out of three serial tests, therapy consists of tight glycemic control, blood pressure control, and the use of ACE-inhibitor medications (titrated to the maximum tolerated dose). The same therapy is applied if a patient’s creatinine is elevated into the range of chronic kidney disease (using the MDRD formula — see references for further information (1,2). Smoking cessation and control of high cholesterol (if appropriate medications are available) may also help slow or prevent progression of nephrotic disease. After initial diagnosis, diabetic patients should have screening with a serum creatinine and urine screening for albumin on annual basis as their finances and clinic resources allow.

Diabetic retinopathy should be screened for with fundoscopy, and is managed with control of blood glucose levels, blood pressure, and referral to an ophthalmologist when possible. Where available, referral to an optometrist or ophthalmologist for screening every two to three years is recommended (2), as a dilated exam by an experienced provider has the best chance of discovering this complication. Fundoscopy should also be performed in the above situation, as long you feel comfortable looking for the signs of diabetic retinopathy.

Finally, diabetic neuropathy screening is important for the prevention of foot infections – this is screened for using sensation to vibration (128 Hz tuning fork, typically the earliest sign of peripheral neuropathy) or sensation to a monofilament, if available (1). The presence or absence of foot pulses is another important aspect of the diabetic foot exam, as both peripheral neuropathy and vasculopathy can lead to an increased rate of foot ulcers. If sensation is diminished, or pulses absent, it is important to advise the patient on appropriate foot care (wearing shoes, closely monitoring for breakdown in the skin) to avoid the formation of ulcers and the potentially limb- and life-threatening complications of diabetic foot ulcer (1). The discussion of further neurological complications (treatment of painful diabetic neuropathy, erectile dysfunction, gastoparesis, autonomic dysfunction) is beyond the scope of this case, but is reviewed by the IDF and ADA in their guidelines (1,2).

Incorrect Choices:

Kidney disease, by measuring a serum creatinine and testing for albuminuria

The authors disagree.This is an important part of screening for diabetes complications, but is not sufficient by itself.

Neuropathy, with a foot examination including vibration sensation and monofilament testing

The authors disagree.This is an important part of screening for diabetes complications, but is not sufficient by itself.

Heart disease, with a stress test

The authors disagree.While diabetics are at increased risk of heart disease, including asymptomatic heart attacks, there is no role presently known for stress tests in asymptomatic patients in any setting. Macrovascular disease (coronary heart disease, peripheral artery disease, cerebrovascular disease) is best screened via a history: ask patients about anginal symptoms, symptoms of heart failure, claudication, and whether they have previously had symptoms of possible stroke or myocardial infarction. Prevention decisions for macrovascular disease can be assisted by calculation of risk using an online calculator. Additionally, an EKG where available can be checked for pathological q waves, which would suggest a likely prior myocardial infarction and a high risk for subsequent complications.

The ADA recommends checking cholesterol levels on an annual year where possible, as this is a risk factor for cardiovascular disease (along with smoking, hypertension, and a family history of heart disease or stroke).

In settings such as Haiti where cholesterol testing is often not readily available, diabetics with any other cardiac risk factor (family history of early heart attacks, smoking, hypertension, proteinuria, women aged > 65 or men > 50) can be considered high risk and given aspirin (81mg once a day). If statin drugs are available, they should be given with a goal of LDL < 100 mg/dL for patients without known cardiovascular disease (<70 mg/dL goal for those with cardiovascular disease), or statins can be provided to all high risk patients if cholesterol testing is not available. Blood pressure should be controlled as discussed later; all smoking patients should be strongly urged to quit (1,2).

Compare Your Answer

Case Follow-Up

At your next visit three weeks later, Mrs. S. is feeling much better. She has reduced the amount of carbohydrates in her diet by avoiding sweet fruit and plantains, and also increased the amount of walking she does each day. She is taking her metformin as prescribed without problems, now up to 1,000 mg twice a day. A community health worker from your clinic has visited her twice to check her blood glucose, and found values of 110 mg/dL (fasting) and 150 mg/dL (after meal).

On repeat visit, her blood pressure is now 144/72; her fasting glucose is 125 mg/dL, which is at goal.

You have read that the risk of death from cardiac causes is elevated in diabetic patients by at least two-fold, so you are carefully watching her blood pressure.

Question 3 of 4

What are the blood pressure goals for a diabetic patient? What agent should you use for management of blood pressure initially if Mrs. S. needed one?

Correct Choices:

Blood pressure goal of <140/<90; initial agent of lisinopril (or other ACE-inhibitor) if needed

The answer is correct.It is important that Mrs. S. have reasonable control of her blood pressure, given the markedly higher rates of stroke and heart attack in a diabetic population. Many guidelines would advocate for a blood pressure target of <130/80 (1); however, some studies have shown no benefit, or possibly increased harm, when targeting such blood pressure ranges. A conservative target with proven benefit is <140/90 (2). If her blood pressure is greater than this goal on two separate occasions after she has instituted lifestyle changes (increased exercise, decreased salt in diet), she should be started on anti-hypertensive medications. For some patients, especially younger patients, a more stringent goal of <130/80 may be appropriate.

ACE-inhibitors or ARBs are the preferred agent for any patient with proteinuria, as there is strong evidence that they reduce the risk of diabetic nephropathy. They may also provide a slight reduction in overall sugars, whereas thiazide diuretics may actually increase sugars. Many providers therefore use ACE-inhibitors or ARBs as their first-line drugs for all hypertensive diabetics, and guidelines support this decision. For a second agent or for those circumstances where ACE-inhibitors or ARBs are unavailable, diuretics, calcium channel blockers, and beta blockers are all appropriate medication choices (1,2).

Incorrect Choices:

Blood pressure goal of <140/<90; initial agent of hydrochlorothiazide (or other thiazide diuretic) if needed

The authors disagree.Thiazide diuretics are not the preferred blood pressure agents for diabetics. A blood pressure goal of <140/90 is reasonable, however.

Provide all patients with lisinopril (or other ACE-inhibitor) regardless of blood pressure

The authors disagree.While ACE-inhibitors or ARBs are indicated for all hypertensive diabetics and all diabetics with proteinuria, it is not recommended that they be given for primary prevention to all patients with diabetes.

Provide patients with hydrochlorothiazide (or other thiazide diuretic) regardless of blood pressure

The authors disagree.Hydrochlorothiazide (HCTZ) is not the preferred first-line agent for treating blood pressure in diabetics, due to the benefits of ACE-inhibitors and ARB medications in reducing diabetic nephropathy. That said, if Mrs. S. could not tolerate an ACE-I or ARB, or if those medications were not available at your clinic, HCTZ would then be an acceptable medication choice if her blood pressure was elevated (>140/90).

Question 4 of 4

Mrs. S. is also curious whether her children are at increased risk for type 2 diabetes. What is an appropriate approach to screening her family for diabetes.

Correct Choices:

Her children should be screened depending on what risk factors they have for diabetes, and the risk factors that result in them being screened will vary depending on the resources available to the clinic

This answer is correct.All patients with symptoms of hyperglycemia should be tested for diabetes – this is not screening, but diagnosis. Symptoms consistent with hyperglycemia include dehydration, frequent urination, increased appetite, increased thirst, and weight loss.

Diagnosis and screening alike can be with a HbA_1c, a random plasma glucose, a fasting glucose, an oral glucose tolerance test, or with a urine dipstick for glucosuria (the latter should only be used if the other options are prohibitively expensive); each clinic or hospital should have a policy regarding what test they will use, as there are tradeoffs involved with each (1).

Beyond this, however, there is benefit to screening some patients for diabetes in an attempt to diagnose them early, either because they are at increased risk to develop type 2 diabetes or because they have other diseases that place them at higher risk of complications should they have undiagnosed diabetes. Different guidelines suggest different risk factors for screening a patient for diabetes; the American Diabetes Association suggests screening patients with following characteristics:

Age 45 years or older.
Overweight (BMI equal to or great than 25) and a comorbid disease (cardiovascular disease, hypertension, low HDL, high LDL) or a risk factor that increases the likelihood of diabetes (first-degree relative with diabetes, physical inactive, mother with gestational diabetes, women with polycystic ovary syndrome, prediabetes, severe obesity, acanthosis nigricans on examination).For those with a negative screen, the ADA recommends repeating it at least every three years.
The International Diabetes Federation guidelines recognize that this amount of screening may not be possible in a resource-limited setting due to the costs imposed, and recommend that screening be limited to “very high-risk” individuals. Different locations in Haiti may have different criteria, therefore; one possible approach would be to screen patients with hypertension, cardiovascular disease, and chronic kidney disease as those who have a high risk of severe complications impacted by the presence of diabetes, as has been proposed for other resource-limited settings (4).

Incorrect Choices:

All of her children should be screened, since they have a family member with diabetes

The authors disagree.Type 2 diabetes does have a large genetic component, and many diabetics have a family member who is also diabetic. In a study done in America, children of diabetics had a 40% chance of developing diabetes themselves by age 60 (3). It is not possible to say what risk Mrs. S.’ children have, though we know it is higher than the general population.

While there is no need for specific screening for them just because a family member of theirs has diabetes, it does count as a risk factor when considering whether they should be screened, and by ADA guidelines any of them who are overweight (BMI equal to or greater than 25) should be screened (2).

You tell her that you screen all patients

The authors disagree.This is not recommended in any setting presently (1, 2), due to the high cost of universal screening, and the uncertain benefit of diagnosing patients earlier in the course of their disease. The benefits of treating diabetes are best established in trials for those patients who presented with symptoms causing them to be diagnosed. That said, there are some groups of patients who likely benefit from earlier diagnosis and treatment.

Only a patient with symptoms of hyperglycemia, like her, needs to be tested for diabetes

The authors disagree.This answer is not entirely wrong, but it is not the best answer. It is certainly true that patients who have symptoms of hyperglycemia should be tested for diabetes. However, there are other populations of patients who are at high risk for diabetes or complications for diabetes who should also be screened should the resources of the health system allow it.

Summary

1. In low-resource settings such as Haiti, the initial management of newly diagnosed Type 2 diabetics (after any initial stabilization required for markedly hyperglycemic patients or patients with kidney damage) will often be with oral medications, depending on the ability of the patient and health system to use insulin safely. Metformin is the first-line medication, while the sulfonylureas are an alternative for patients who cannot tolerate metformin. If adequate control cannot be obtained on the maximum dose of one class of medications, the other class should be added. All patients should be advised on appropriate diet and exercise.

2. Diabetic patients should be screened annually if possible for kidney disease with urine albumin (or dipstick for protein if unavailable) and serum creatinine); peripheral neuropathy; and for diabetic foot disease. If possible, screening for retinal diseases should also be done at least every two years.

3. Diabetic patients should have their blood pressure checked at every clinic appointment; a target blood pressure of <140/<90 is reasonable, with a lower goal of <130/<80 for select patients. Patients with blood pressure elevations above this should be initiated on therapy, and the first-line medication should be an ACE-inhibitor or ARB.

4. The glycemic control target in a low-resource setting can reasonably be set at an HbA1c goal of 7% or less (or a fasting glucose of equal to or less than 130 if HbA_1c measurement is not available). Lower or higher goals can be set depending on individual patients’ clinical and social characteristics.

5. Diabetic patients at high risk for stroke and myocardial infarction should be started on an aspirin and, if available, a statin. Risk can be determined by online calculators with cholesterol testing. If cholesterol testing is not available, patients any of the following risk factors can be considered high risk: family history of early heart attacks (before 60), smoking, hypertension, proteinuria, women aged >65 and men >50.

6. All patients with hypertension and chronic kidney disease should be screened for diabetes, as should any patients with symptoms potentially attributable to diabetes. If resources allow, it is also reasonable to screen obese relatives of known diabetics and other delineated groups as per the ADA guidelines.

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Question 1 of 4 What is the most reasonable initial management of your patient’s diabetes, within the Haitian context?

		a.	Insulin on a weight-based regimen along with counseling on diet and exercise The authors disagree.The International Diabetes Federation and American Diabetes Association guidelines (1,2) both recommend the initiation of insulin when maximal oral agents have failed to provide adequate glycemic control, or sooner as clinically indicated (for example, a patient with an hemoglobin HbA_1c of 11% would be very unlikely to obtain adequate glycemic control with diet, exercise, and oral agents only). For this Haitian patient, while insulin initiation is not contraindicated, it raises substantially more challenges than oral medication for both the physician as well as for the patient. Insulin requires at least daily (often more frequent) injections with sterile needles, daily blood glucose testing, intensive education on the proper use of insulin and the warning signs of hypoglycemia, as well as a reliably cool (ideally refrigerated) location for insulin storage. This patient has limited financial resources, and lacks a refrigerator in particular. While insulin is very effective, due to the difficulties and costs in implementing its use in Haiti, it is worth trying oral medications first (which can also be very effective), along with diet and exercise counseling (which applies to all diabetic patients). The point at which to start insulin will vary depending on the resources available at your clinic and the resources of the patient in question. For Mrs. S., while she may eventually require insulin, initially she may do well with oral agents alone. Because she demonstrates no signs of pronounced hypovolemia, acidosis or renal impairment, she is not in any immediate danger of hyperosmotic sequelae, which would necessitate at least temporary insulin use and possibly hospitalization.
		b.	Metformin twice a day along with counseling on diet and exercise The answer is correct.Mrs. S. will need a thorough discussion about diabetes, how it is treated, and why it is important to continue with these therapies even once she feels better. If her glucose was very elevated (to the >300 range) and she had signs of hypovolemia, or if she had acidosis with or without renal impairments on her labs, treatment with insulin and intravenous fluids to rapidly correct her blood glucose and prevent complications would be indicated. Mrs. S. does not appear to be dehydrated on exam, so she may be told to increase her intake of non-sugary fluids for a few days, and started on metformin. She should also be advised on increasing her exercise (for example, walking for an hour every evening), and on specifics of an appropriate diet (see answer C for more information on diet). The use of oral medications to lower blood glucose has been shown in a number of trials to reduce the risk of diabetic complications; it may also reduce the risk of death in some populations, though this effect has not been demonstrated as thoroughly (1). In general, metformin is presently the preferred starting medication for most (BMI of 25 or greater) patients with type 2 diabetes (1,2) who do not require insulin. When compared to other medications in trials, metformin is associated with essentially no hypoglycemia, less weight gain (often weight loss, in fact), and potentially a greater reduction in the risk for complications of diabetes. Due to a rare risk of lactic acidosis, it should be used cautiously in patients with impaired kidney function (estimate glomerular filtration rate of equal to or less than 45 ml/min/1.73 m²) (1). It often causes diarrhea, abdominal cramping, and nausea/vomiting. These symptoms usually wane with time, and can be reduced by starting with a low dose (500mg once or twice a day, taken with food) and increasing the dose over several weeks (maximum of 2500 mg/day, split into two to three doses). Mrs. S. should be warned about these adverse effects and the importance of taking the medicines should be emphasized. The glycemic control goal, depending on the guidelines used, is to aim for a HbA_1c of 7% or less (1, 2), or a fasting plasma glucose of <115 mg/dL (1) or 70-130 mg/dL (2), or a plasma glucose two hours after a meal of <160 mg/dL (1) or <180 mg/dL (2). In a low-resource setting such as Haiti, where more intensive monitoring is not possible, where the dangers of hypoglycemia are higher, and where the long-term benefits of ultra-aggressive glycemic control are unclear, a HbA_1c goal of 7% is a reasonable target; Table 1 shows the correlation between HbA1c and the average sugar through the day. If HbA_1c cannot be measured, a fasting plasma glucose can be substituted as a crude alternative (in which case the goal of a fasting plasma glucose <130 (mg/dL) would be the target); note that HbA_1c is the preferred lab test to monitor long-term glycemic control whenever possible, and that fasting plasma glucose values can be skewed by prior meals, exercise, and infection. Because it is a long-term measure, HbA_1c when avaiable should only be checked every three months (2). Should Mrs. S. ever have low sugars or if there are difficulties in monitoring her sugars, more relaxed goals are reasonable to set, particularly when using agents that can cause hypoglycemia. If she cannot reach her glycemic target after a maximal dose of metformin for several months, a sulfonylurea can be added to her regimen. Table 1. Estimated average blood glucose based on hemoglobin A_1c percent. Adapted from The American Diabetes Association.
		c.	Advice on a diabetic diet and encouraging exercise alone The authors disagree.This is an important part of managing any patient with diabetes. All clinics and hospitals should have staff who can discuss the importance with patients of managing their diet to reduce simple carbohydrates (white rice, beans, sugar, sodas, juices, fruits, white potatoes, plantains) and increase the amount of complex carbohydrates, vegetables, and proteins. Similarly, patients who do not have an active lifestyle should be encouraged to engage in exercise (such as walking for 30 minutes every day). Unfortunately, given how high her glucose is, diet and exercise alone are very unlikely to reduce her rangesblood sugars adequately. Moreover, the ADA guidelines (2) recommend that any patient diagnosed with diabetes be started on a medical therapy, typically metformin or, if very poorly controlled, insulin (see other answers for further discussion).
		d.	Glipizide or another sulfonylurea, once a day before her largest meal, along with counseling on diet and exercise The authors disagree.Metformin is the oral agent of choice for most patients, though a sulfonylurea can be used as an alternative if clinically indicated, or if metformin is unavailable (1,2). Glibenclamide is the WHO-recommended sulfonylurea. These agents have a real risk of hypoglycemia (unlike metformin), and should be used with caution in patients with impaired function of the kidneys or liver, as these increase the risk of hypoglycemia. Dosing depends on the sulfonylurea being used, but would typically start with once a day before the largest meal of the day.

Question 2 of 4What complications of diabetes should you screen for?

		a.	Kidney disease, by measuring a serum creatinine and testing for albuminuria The authors disagree.This is an important part of screening for diabetes complications, but is not sufficient by itself.
		b.	Neuropathy, with a foot examination including vibration sensation and monofilament testing The authors disagree.This is an important part of screening for diabetes complications, but is not sufficient by itself.
		c.	Kidney disease, neuropathy, and retinopathy The answer is correct.The complications of diabetes are divided into microvascular and macrovascular in nature. Microvascular disease affects a number of organs, notably the kidneys, the eyes, and the nervous system. Since all of these complications are typically asymptomatic at first, all newly diagnosed diabetics should have all of the screening tests recommended below. Kidney disease should be screened for with a serum creatinine as well as a urine testing looking for protein (ideally a test specific for microalbuminuria, which is much more sensitive than a generic urine dipstick) – if protein is found on urine testing, urinary tract infection should be ruled out and the test repeated, ideally with urinary albumin/creatinine or urinary protein/creatinine testing. If proteinuria is confirmed on two out of three serial tests, therapy consists of tight glycemic control, blood pressure control, and the use of ACE-inhibitor medications (titrated to the maximum tolerated dose). The same therapy is applied if a patient’s creatinine is elevated into the range of chronic kidney disease (using the MDRD formula — see references for further information (1,2). Smoking cessation and control of high cholesterol (if appropriate medications are available) may also help slow or prevent progression of nephrotic disease. After initial diagnosis, diabetic patients should have screening with a serum creatinine and urine screening for albumin on annual basis as their finances and clinic resources allow. Diabetic retinopathy should be screened for with fundoscopy, and is managed with control of blood glucose levels, blood pressure, and referral to an ophthalmologist when possible. Where available, referral to an optometrist or ophthalmologist for screening every two to three years is recommended (2), as a dilated exam by an experienced provider has the best chance of discovering this complication. Fundoscopy should also be performed in the above situation, as long you feel comfortable looking for the signs of diabetic retinopathy. Finally, diabetic neuropathy screening is important for the prevention of foot infections – this is screened for using sensation to vibration (128 Hz tuning fork, typically the earliest sign of peripheral neuropathy) or sensation to a monofilament, if available (1). The presence or absence of foot pulses is another important aspect of the diabetic foot exam, as both peripheral neuropathy and vasculopathy can lead to an increased rate of foot ulcers. If sensation is diminished, or pulses absent, it is important to advise the patient on appropriate foot care (wearing shoes, closely monitoring for breakdown in the skin) to avoid the formation of ulcers and the potentially limb- and life-threatening complications of diabetic foot ulcer (1). The discussion of further neurological complications (treatment of painful diabetic neuropathy, erectile dysfunction, gastoparesis, autonomic dysfunction) is beyond the scope of this case, but is reviewed by the IDF and ADA in their guidelines (1,2).
		d.	Heart disease, with a stress test The authors disagree.While diabetics are at increased risk of heart disease, including asymptomatic heart attacks, there is no role presently known for stress tests in asymptomatic patients in any setting. Macrovascular disease (coronary heart disease, peripheral artery disease, cerebrovascular disease) is best screened via a history: ask patients about anginal symptoms, symptoms of heart failure, claudication, and whether they have previously had symptoms of possible stroke or myocardial infarction. Prevention decisions for macrovascular disease can be assisted by calculation of risk using an online calculator. Additionally, an EKG where available can be checked for pathological q waves, which would suggest a likely prior myocardial infarction and a high risk for subsequent complications. The ADA recommends checking cholesterol levels on an annual year where possible, as this is a risk factor for cardiovascular disease (along with smoking, hypertension, and a family history of heart disease or stroke). In settings such as Haiti where cholesterol testing is often not readily available, diabetics with any other cardiac risk factor (family history of early heart attacks, smoking, hypertension, proteinuria, women aged > 65 or men > 50) can be considered high risk and given aspirin (81mg once a day). If statin drugs are available, they should be given with a goal of LDL < 100 mg/dL for patients without known cardiovascular disease (<70 mg/dL goal for those with cardiovascular disease), or statins can be provided to all high risk patients if cholesterol testing is not available. Blood pressure should be controlled as discussed later; all smoking patients should be strongly urged to quit (1,2).

Question 3 of 4What are the blood pressure goals for a diabetic patient? What agent should you use for management of blood pressure initially if Mrs. S. needed one?

		a.	Blood pressure goal of <140/<90; initial agent of hydrochlorothiazide (or other thiazide diuretic) if needed The authors disagree.Thiazide diuretics are not the preferred blood pressure agents for diabetics. A blood pressure goal of <140/90 is reasonable, however.
		b.	Blood pressure goal of <140/<90; initial agent of lisinopril (or other ACE-inhibitor) if needed The answer is correct.It is important that Mrs. S. have reasonable control of her blood pressure, given the markedly higher rates of stroke and heart attack in a diabetic population. Many guidelines would advocate for a blood pressure target of <130/80 (1); however, some studies have shown no benefit, or possibly increased harm, when targeting such blood pressure ranges. A conservative target with proven benefit is <140/90 (2). If her blood pressure is greater than this goal on two separate occasions after she has instituted lifestyle changes (increased exercise, decreased salt in diet), she should be started on anti-hypertensive medications. For some patients, especially younger patients, a more stringent goal of <130/80 may be appropriate. ACE-inhibitors or ARBs are the preferred agent for any patient with proteinuria, as there is strong evidence that they reduce the risk of diabetic nephropathy. They may also provide a slight reduction in overall sugars, whereas thiazide diuretics may actually increase sugars. Many providers therefore use ACE-inhibitors or ARBs as their first-line drugs for all hypertensive diabetics, and guidelines support this decision. For a second agent or for those circumstances where ACE-inhibitors or ARBs are unavailable, diuretics, calcium channel blockers, and beta blockers are all appropriate medication choices (1,2).
		c.	Provide all patients with lisinopril (or other ACE-inhibitor) regardless of blood pressure The authors disagree.While ACE-inhibitors or ARBs are indicated for all hypertensive diabetics and all diabetics with proteinuria, it is not recommended that they be given for primary prevention to all patients with diabetes.
		d.	Provide patients with hydrochlorothiazide (or other thiazide diuretic) regardless of blood pressure The authors disagree.Hydrochlorothiazide (HCTZ) is not the preferred first-line agent for treating blood pressure in diabetics, due to the benefits of ACE-inhibitors and ARB medications in reducing diabetic nephropathy. That said, if Mrs. S. could not tolerate an ACE-I or ARB, or if those medications were not available at your clinic, HCTZ would then be an acceptable medication choice if her blood pressure was elevated (>140/90).

Question 4 of 4

Mrs. S. is also curious whether her children are at increased risk for type 2 diabetes. What is an appropriate approach to screening her family for diabetes.

		a.	All of her children should be screened, since they have a family member with diabetes The authors disagree.Type 2 diabetes does have a large genetic component, and many diabetics have a family member who is also diabetic. In a study done in America, children of diabetics had a 40% chance of developing diabetes themselves by age 60 (3). It is not possible to say what risk Mrs. S.’ children have, though we know it is higher than the general population. While there is no need for specific screening for them just because a family member of theirs has diabetes, it does count as a risk factor when considering whether they should be screened, and by ADA guidelines any of them who are overweight (BMI equal to or greater than 25) should be screened (2).
		b.	You tell her that you screen all patients The authors disagree.This is not recommended in any setting presently (1, 2), due to the high cost of universal screening, and the uncertain benefit of diagnosing patients earlier in the course of their disease. The benefits of treating diabetes are best established in trials for those patients who presented with symptoms causing them to be diagnosed. That said, there are some groups of patients who likely benefit from earlier diagnosis and treatment.
		c.	Only a patient with symptoms of hyperglycemia, like her, needs to be tested for diabetes The authors disagree.This answer is not entirely wrong, but it is not the best answer. It is certainly true that patients who have symptoms of hyperglycemia should be tested for diabetes. However, there are other populations of patients who are at high risk for diabetes or complications for diabetes who should also be screened should the resources of the health system allow it.
		d.	Her children should be screened depending on what risk factors they have for diabetes, and the risk factors that result in them being screened will vary depending on the resources available to the clinic This answer is correct.All patients with symptoms of hyperglycemia should be tested for diabetes – this is not screening, but diagnosis. Symptoms consistent with hyperglycemia include dehydration, frequent urination, increased appetite, increased thirst, and weight loss. Diagnosis and screening alike can be with a HbA_1c, a random plasma glucose, a fasting glucose, an oral glucose tolerance test, or with a urine dipstick for glucosuria (the latter should only be used if the other options are prohibitively expensive); each clinic or hospital should have a policy regarding what test they will use, as there are tradeoffs involved with each (1). Beyond this, however, there is benefit to screening some patients for diabetes in an attempt to diagnose them early, either because they are at increased risk to develop type 2 diabetes or because they have other diseases that place them at higher risk of complications should they have undiagnosed diabetes. Different guidelines suggest different risk factors for screening a patient for diabetes; the American Diabetes Association suggests screening patients with following characteristics: Age 45 years or older. Overweight (BMI equal to or great than 25) and a comorbid disease (cardiovascular disease, hypertension, low HDL, high LDL) or a risk factor that increases the likelihood of diabetes (first-degree relative with diabetes, physical inactive, mother with gestational diabetes, women with polycystic ovary syndrome, prediabetes, severe obesity, acanthosis nigricans on examination).For those with a negative screen, the ADA recommends repeating it at least every three years. The International Diabetes Federation guidelines recognize that this amount of screening may not be possible in a resource-limited setting due to the costs imposed, and recommend that screening be limited to “very high-risk” individuals. Different locations in Haiti may have different criteria, therefore; one possible approach would be to screen patients with hypertension, cardiovascular disease, and chronic kidney disease as those who have a high risk of severe complications impacted by the presence of diabetes, as has been proposed for other resource-limited settings (4).

References

1. International Diabetes Federation, Global Guideline for Type 2 Diabetes. 2012.

2. American Diabetes Association. Standards of Medical Care in Diabetes—2013. Diabetes Care; January 2013 34:S11-S66.

3. Tattersal RB and Fajans SS. Prevalence of diabetes and glucose intolerance in 199 offspring of thirty-seven conjugal diabetic parents. Diabetes; 1975, 24(5): 452-62.

4. “Diabetes.” In: The PIH Guide to Chronic Care Integration for Endemic Non-Communicable Diseases, G Bukhman and A Kidder eds.

Posttest

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DIABETES POSTTEST

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Last name

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In settings where hemoglobin A1C measurement is not available, what should be the fasting glucose goal in patients being treated for diabetes?

	Below 90 g/dL
	Below 130 g/dL
	Below 150 g/dL
	Below 200 g/dL

Which of the following medications is not associated with a significant risk of hypoglycemia?

	Insulin
	Glibenclamide
	Metformin
	Glipizide

Diet changes and exercise have been shown to lower HbA1C values by up to how much?

	0.3%
	1%
	1.5%
	2%

What is the best initial medication for diabetic patients with severe renal impairment (eg, GFR less than 30 ml/min/1.73 m2) ?

	Insulin
	Glibenclamide
	Metformin
	None of these medications are safe in patients with severe renal impairment

Which of the following classes of medication is generally preferred as the first-line therapy for the treatment of hypertension in diabetic patients?

	Beta blockers
	Thiazide diuretics
	ACE inhibitors
	Calcium channel blockers

* Required Field

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