Clinical Review

The effects of breast cancer on obstetric and gynecologic practices are pervasive. In this article, we touch on three aspects of breast cancer that are particularly relevant to the practicing ObGyn:

• the need to identify women at high risk for breast cancer and select those who would benefit from a discussion of the advantages and risks of chemoprophylaxis, which can reduce the likelihood of breast cancer by 50% or more
• the need for strategies to manage menopausal symptoms in the general population without increasing the risk of breast cancer. The traditional approach to this problem changed dramatically with the Women’s Health Initiative (WHI), which demonstrated an increased risk of breast cancer in women taking conjugated equine estrogen and progestin. The widely publicized initial findings of the estrogen-progestin arm of the WHI sharply contrast the equally relevant, somewhat unexpected, and less publicized results of the estrogen-alone arm, which demonstrated a substantial and statistically significant decrease in the incidence of breast cancer, even after estrogen was discontinued.
• the potential effects of breast cancer treatment on ovarian function in young women. This year, of the approximately 250,000 women who will be diagnosed with invasive breast cancer, more than 50,000 women will be of reproductive age. Most of these young women will require adjuvant chemotherapy; as a result, many will experience the premature onset of menopause. Along with the attendant loss of fertility these women will face, many will also develop distressing and life-altering menopausal symptoms. Management of these women before and after initiation of chemotherapy requires an understanding of both the expected effects of the chemotherapy and knowledge of how to actively manage these women with strategies to either prevent these events or to manage menopausal symptoms.

In women at normal risk for breast cancer, unopposed estrogen lowers the rate of the malignancy and the likelihood of mortality if the cancer occurs—but is not recommended as a prophylactic agent. Tamoxifen and other chemoprophylactic drugs can halve the rate of breast cancer in high-risk women but are not without drawbacks.

A look at the lower rate of breast cancer in the estrogen-alone arm of the WHI

Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

From 1993 through 1998, the WHI enrolled 10,739 postmenopausal women in the largest prospective trial evaluating the effect of hormone therapy (HT) on various clinical outcomes. The women were randomly allocated to three groups:

• conjugated estrogen with medroxyprogesterone acetate
• conjugated estrogen alone (in women with a prior hysterectomy)
• placebo.

The negative effects of estrogen plus progestin on the risk of breast cancer were the most widely discussed oucomes.¹ Shortly after the findings from this arm of the study were published, the use of HT in the United States declined dramatically and unequivocally.²

In 2012, WHI published the results of the estrogen-alone arm in the British cancer specialty journal Lancet Oncology. As shown in the TABLE below, the incidence of breast cancer was statistically significantly lower (23%) in the estrogen group than in the placebo group. Women who were treated with estrogen alone were also 63% less likely to die of breast cancer, and all-cause mortality was 38% lower; both of these findings were statistically significant. Not only was there a significant reduction in the incidence of invasive breast cancer while the subjects were taking estrogen, but that reduction continued for a median of 4.7 years of follow-up after discontinuation of estrogen.

Breast cancer incidence and mortality in the estrogen-only arm of the WHI, compared with placebo*

The incidence figure is somewhat remarkable (199 in the placebo group versus 151 in the estrogen-alone group) in that it was nearly the exact reverse of the estrogen-progestin arm of the WHI trial (199 in the estrogen/progestin group vs 150 in the placebo group).³

All breast cancer chemoprophylactic agents carry risks as well as benefits

Goss P, Ingle J, Ales-Martinez J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381–2391.

Cheung A, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomized controlled trial. Lancet Oncol. 2012;13(3):275–284.

Vogel V, Costantino J, Wickerham L, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res. 2010;3(6):696–706.

The number of new cases of breast cancer in the United States last year reached nearly a quarter-million. Clearly, reducing this number remains an important goal.⁴ Chemoprevention—the use of medication to reduce cancer risk—may be offered to women who are at high risk of developing breast cancer.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen (a selective estrogen-receptor modulator) was shown to reduce the risk of invasive breast cancer by 49% in a high-risk population, resulting in the FDA approving tamoxifen as the first drug for breast cancer prevention.⁵ The P-1 trial was followed by the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial, which demonstrated relative equivalence between the two medications as cancer prevention agents in menopausal women.⁶ Serious side effects of these medications limit their use among eligible women, although raloxifene seems to be associated with fewer adverse events. In the update of the STAR trial with an average of 81 months of follow-up, the risk ratio for adverse events (raloxifene:tamoxifen) was 0.75 for thromboembolic events, 0.55 for endometrial cancer, and 0.19 for uterine hyperplasia.

Another drug used for cancer treatment has now entered the prevention scene. In 2011, the NCIC Clinical Trials Group Mammary Prevention.3 trial (NCIC CTG MAP.3) compared exemestane (an aromatase inhibitor) with placebo for menopausal women at high risk for breast cancer, demonstrating a 65% relative reduction in the incidence of invasive breast cancer. This study validated another option for cancer prevention in high-risk women, although its adoption is likely also to be limited by side effects, including vasomotor symptoms, a high rate of arthralgias, and vaginal dryness/dyspareunia. The greatest concern may be the potential effect on bone density. Though the rates of serious adverse events including fracture did not differ in the MAP.3 trial at 35 months of follow-up, women on exemestane had significantly larger losses of bone mineral density, compared with controls.

Managing the reproductive health concerns of young women with breast cancer

Azim H, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–79.

Howard-Anderson J, Ganz P, Bower J, Stanton A. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(5):1386–1405.

Of the approximately 230,000 new cases of invasive breast cancer identified in 2011, 50,430 cases involved women less than 50 years of age.⁴ For these women, the diagnosis of cancer raises multifaceted concerns, including the physical changes that accompany breast cancer treatment, concerns about recurrence and mortality, and significant sexual and reproductive consequences of treatment that alters ovarian function. Pregnancy-associated breast cancers (breast cancers diagnosed during pregnancy, lactation, and for 12 months postpartum) represent a small subset of these cancers and occur in about 1 in 3,000 pregnancies. One might anticipate that this rate will increase as women continue to delay childbearing, because pregnancy-associated breast cancers are more common in older women.

In the review article by Howard-Anderson and colleagues, the importance of these reproductive health consequences in young women diagnosed with breast cancer is highlighted. The women who transition to menopause as a result of chemotherapy (reported to range from 33%–73%) experience more symptoms, including hot flashes, night sweats, breast pain, vaginal dryness, and lack of sexual desire. Sixty-one percent of women younger than 40 years at diagnosis reported that they were concerned about menopause, and 30% reported that this concern influenced their treatment decisions. Thirty-nine percent of women in this group had major concerns about treatment-associated infertility, and only half of the women studied felt that their fertility concerns were adequately addressed.

On a positive note, for women who successfully achieve pregnancy after breast cancer, pregnancy outcomes appear to be similar to those of their nonpregnant peers. In the study by Azim and colleagues, women who became pregnant after a breast cancer diagnosis had disease-free survival that was statistically similar to that of matched women who did not have subsequent pregnancies. In addition, this outcome did not differ based on estrogen/progesterone receptor status (ER/PR positive or negative).

We want to hear from you! Tell us what you think.

The effects of breast cancer on obstetric and gynecologic practices are pervasive. In this article, we touch on three aspects of breast cancer that are particularly relevant to the practicing ObGyn:

• the need to identify women at high risk for breast cancer and select those who would benefit from a discussion of the advantages and risks of chemoprophylaxis, which can reduce the likelihood of breast cancer by 50% or more
• the need for strategies to manage menopausal symptoms in the general population without increasing the risk of breast cancer. The traditional approach to this problem changed dramatically with the Women’s Health Initiative (WHI), which demonstrated an increased risk of breast cancer in women taking conjugated equine estrogen and progestin. The widely publicized initial findings of the estrogen-progestin arm of the WHI sharply contrast the equally relevant, somewhat unexpected, and less publicized results of the estrogen-alone arm, which demonstrated a substantial and statistically significant decrease in the incidence of breast cancer, even after estrogen was discontinued.
• the potential effects of breast cancer treatment on ovarian function in young women. This year, of the approximately 250,000 women who will be diagnosed with invasive breast cancer, more than 50,000 women will be of reproductive age. Most of these young women will require adjuvant chemotherapy; as a result, many will experience the premature onset of menopause. Along with the attendant loss of fertility these women will face, many will also develop distressing and life-altering menopausal symptoms. Management of these women before and after initiation of chemotherapy requires an understanding of both the expected effects of the chemotherapy and knowledge of how to actively manage these women with strategies to either prevent these events or to manage menopausal symptoms.

In women at normal risk for breast cancer, unopposed estrogen lowers the rate of the malignancy and the likelihood of mortality if the cancer occurs—but is not recommended as a prophylactic agent. Tamoxifen and other chemoprophylactic drugs can halve the rate of breast cancer in high-risk women but are not without drawbacks.

A look at the lower rate of breast cancer in the estrogen-alone arm of the WHI

Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

From 1993 through 1998, the WHI enrolled 10,739 postmenopausal women in the largest prospective trial evaluating the effect of hormone therapy (HT) on various clinical outcomes. The women were randomly allocated to three groups:

• conjugated estrogen with medroxyprogesterone acetate
• conjugated estrogen alone (in women with a prior hysterectomy)
• placebo.

The negative effects of estrogen plus progestin on the risk of breast cancer were the most widely discussed oucomes.¹ Shortly after the findings from this arm of the study were published, the use of HT in the United States declined dramatically and unequivocally.²

In 2012, WHI published the results of the estrogen-alone arm in the British cancer specialty journal Lancet Oncology. As shown in the TABLE below, the incidence of breast cancer was statistically significantly lower (23%) in the estrogen group than in the placebo group. Women who were treated with estrogen alone were also 63% less likely to die of breast cancer, and all-cause mortality was 38% lower; both of these findings were statistically significant. Not only was there a significant reduction in the incidence of invasive breast cancer while the subjects were taking estrogen, but that reduction continued for a median of 4.7 years of follow-up after discontinuation of estrogen.

Breast cancer incidence and mortality in the estrogen-only arm of the WHI, compared with placebo*

The incidence figure is somewhat remarkable (199 in the placebo group versus 151 in the estrogen-alone group) in that it was nearly the exact reverse of the estrogen-progestin arm of the WHI trial (199 in the estrogen/progestin group vs 150 in the placebo group).³

All breast cancer chemoprophylactic agents carry risks as well as benefits

Goss P, Ingle J, Ales-Martinez J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381–2391.

Cheung A, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomized controlled trial. Lancet Oncol. 2012;13(3):275–284.

Vogel V, Costantino J, Wickerham L, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res. 2010;3(6):696–706.

The number of new cases of breast cancer in the United States last year reached nearly a quarter-million. Clearly, reducing this number remains an important goal.⁴ Chemoprevention—the use of medication to reduce cancer risk—may be offered to women who are at high risk of developing breast cancer.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen (a selective estrogen-receptor modulator) was shown to reduce the risk of invasive breast cancer by 49% in a high-risk population, resulting in the FDA approving tamoxifen as the first drug for breast cancer prevention.⁵ The P-1 trial was followed by the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial, which demonstrated relative equivalence between the two medications as cancer prevention agents in menopausal women.⁶ Serious side effects of these medications limit their use among eligible women, although raloxifene seems to be associated with fewer adverse events. In the update of the STAR trial with an average of 81 months of follow-up, the risk ratio for adverse events (raloxifene:tamoxifen) was 0.75 for thromboembolic events, 0.55 for endometrial cancer, and 0.19 for uterine hyperplasia.

Another drug used for cancer treatment has now entered the prevention scene. In 2011, the NCIC Clinical Trials Group Mammary Prevention.3 trial (NCIC CTG MAP.3) compared exemestane (an aromatase inhibitor) with placebo for menopausal women at high risk for breast cancer, demonstrating a 65% relative reduction in the incidence of invasive breast cancer. This study validated another option for cancer prevention in high-risk women, although its adoption is likely also to be limited by side effects, including vasomotor symptoms, a high rate of arthralgias, and vaginal dryness/dyspareunia. The greatest concern may be the potential effect on bone density. Though the rates of serious adverse events including fracture did not differ in the MAP.3 trial at 35 months of follow-up, women on exemestane had significantly larger losses of bone mineral density, compared with controls.

Managing the reproductive health concerns of young women with breast cancer

Azim H, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–79.

Howard-Anderson J, Ganz P, Bower J, Stanton A. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(5):1386–1405.

Of the approximately 230,000 new cases of invasive breast cancer identified in 2011, 50,430 cases involved women less than 50 years of age.⁴ For these women, the diagnosis of cancer raises multifaceted concerns, including the physical changes that accompany breast cancer treatment, concerns about recurrence and mortality, and significant sexual and reproductive consequences of treatment that alters ovarian function. Pregnancy-associated breast cancers (breast cancers diagnosed during pregnancy, lactation, and for 12 months postpartum) represent a small subset of these cancers and occur in about 1 in 3,000 pregnancies. One might anticipate that this rate will increase as women continue to delay childbearing, because pregnancy-associated breast cancers are more common in older women.

In the review article by Howard-Anderson and colleagues, the importance of these reproductive health consequences in young women diagnosed with breast cancer is highlighted. The women who transition to menopause as a result of chemotherapy (reported to range from 33%–73%) experience more symptoms, including hot flashes, night sweats, breast pain, vaginal dryness, and lack of sexual desire. Sixty-one percent of women younger than 40 years at diagnosis reported that they were concerned about menopause, and 30% reported that this concern influenced their treatment decisions. Thirty-nine percent of women in this group had major concerns about treatment-associated infertility, and only half of the women studied felt that their fertility concerns were adequately addressed.

On a positive note, for women who successfully achieve pregnancy after breast cancer, pregnancy outcomes appear to be similar to those of their nonpregnant peers. In the study by Azim and colleagues, women who became pregnant after a breast cancer diagnosis had disease-free survival that was statistically similar to that of matched women who did not have subsequent pregnancies. In addition, this outcome did not differ based on estrogen/progesterone receptor status (ER/PR positive or negative).

We want to hear from you! Tell us what you think.

The effects of breast cancer on obstetric and gynecologic practices are pervasive. In this article, we touch on three aspects of breast cancer that are particularly relevant to the practicing ObGyn:

• the need to identify women at high risk for breast cancer and select those who would benefit from a discussion of the advantages and risks of chemoprophylaxis, which can reduce the likelihood of breast cancer by 50% or more
• the need for strategies to manage menopausal symptoms in the general population without increasing the risk of breast cancer. The traditional approach to this problem changed dramatically with the Women’s Health Initiative (WHI), which demonstrated an increased risk of breast cancer in women taking conjugated equine estrogen and progestin. The widely publicized initial findings of the estrogen-progestin arm of the WHI sharply contrast the equally relevant, somewhat unexpected, and less publicized results of the estrogen-alone arm, which demonstrated a substantial and statistically significant decrease in the incidence of breast cancer, even after estrogen was discontinued.
• the potential effects of breast cancer treatment on ovarian function in young women. This year, of the approximately 250,000 women who will be diagnosed with invasive breast cancer, more than 50,000 women will be of reproductive age. Most of these young women will require adjuvant chemotherapy; as a result, many will experience the premature onset of menopause. Along with the attendant loss of fertility these women will face, many will also develop distressing and life-altering menopausal symptoms. Management of these women before and after initiation of chemotherapy requires an understanding of both the expected effects of the chemotherapy and knowledge of how to actively manage these women with strategies to either prevent these events or to manage menopausal symptoms.

In women at normal risk for breast cancer, unopposed estrogen lowers the rate of the malignancy and the likelihood of mortality if the cancer occurs—but is not recommended as a prophylactic agent. Tamoxifen and other chemoprophylactic drugs can halve the rate of breast cancer in high-risk women but are not without drawbacks.

A look at the lower rate of breast cancer in the estrogen-alone arm of the WHI

Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

From 1993 through 1998, the WHI enrolled 10,739 postmenopausal women in the largest prospective trial evaluating the effect of hormone therapy (HT) on various clinical outcomes. The women were randomly allocated to three groups:

• conjugated estrogen with medroxyprogesterone acetate
• conjugated estrogen alone (in women with a prior hysterectomy)
• placebo.

The negative effects of estrogen plus progestin on the risk of breast cancer were the most widely discussed oucomes.¹ Shortly after the findings from this arm of the study were published, the use of HT in the United States declined dramatically and unequivocally.²

In 2012, WHI published the results of the estrogen-alone arm in the British cancer specialty journal Lancet Oncology. As shown in the TABLE below, the incidence of breast cancer was statistically significantly lower (23%) in the estrogen group than in the placebo group. Women who were treated with estrogen alone were also 63% less likely to die of breast cancer, and all-cause mortality was 38% lower; both of these findings were statistically significant. Not only was there a significant reduction in the incidence of invasive breast cancer while the subjects were taking estrogen, but that reduction continued for a median of 4.7 years of follow-up after discontinuation of estrogen.

Breast cancer incidence and mortality in the estrogen-only arm of the WHI, compared with placebo*

The incidence figure is somewhat remarkable (199 in the placebo group versus 151 in the estrogen-alone group) in that it was nearly the exact reverse of the estrogen-progestin arm of the WHI trial (199 in the estrogen/progestin group vs 150 in the placebo group).³

All breast cancer chemoprophylactic agents carry risks as well as benefits

Goss P, Ingle J, Ales-Martinez J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381–2391.

Cheung A, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomized controlled trial. Lancet Oncol. 2012;13(3):275–284.

Vogel V, Costantino J, Wickerham L, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res. 2010;3(6):696–706.

The number of new cases of breast cancer in the United States last year reached nearly a quarter-million. Clearly, reducing this number remains an important goal.⁴ Chemoprevention—the use of medication to reduce cancer risk—may be offered to women who are at high risk of developing breast cancer.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen (a selective estrogen-receptor modulator) was shown to reduce the risk of invasive breast cancer by 49% in a high-risk population, resulting in the FDA approving tamoxifen as the first drug for breast cancer prevention.⁵ The P-1 trial was followed by the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial, which demonstrated relative equivalence between the two medications as cancer prevention agents in menopausal women.⁶ Serious side effects of these medications limit their use among eligible women, although raloxifene seems to be associated with fewer adverse events. In the update of the STAR trial with an average of 81 months of follow-up, the risk ratio for adverse events (raloxifene:tamoxifen) was 0.75 for thromboembolic events, 0.55 for endometrial cancer, and 0.19 for uterine hyperplasia.

Another drug used for cancer treatment has now entered the prevention scene. In 2011, the NCIC Clinical Trials Group Mammary Prevention.3 trial (NCIC CTG MAP.3) compared exemestane (an aromatase inhibitor) with placebo for menopausal women at high risk for breast cancer, demonstrating a 65% relative reduction in the incidence of invasive breast cancer. This study validated another option for cancer prevention in high-risk women, although its adoption is likely also to be limited by side effects, including vasomotor symptoms, a high rate of arthralgias, and vaginal dryness/dyspareunia. The greatest concern may be the potential effect on bone density. Though the rates of serious adverse events including fracture did not differ in the MAP.3 trial at 35 months of follow-up, women on exemestane had significantly larger losses of bone mineral density, compared with controls.

Managing the reproductive health concerns of young women with breast cancer

Azim H, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–79.

Howard-Anderson J, Ganz P, Bower J, Stanton A. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(5):1386–1405.

Of the approximately 230,000 new cases of invasive breast cancer identified in 2011, 50,430 cases involved women less than 50 years of age.⁴ For these women, the diagnosis of cancer raises multifaceted concerns, including the physical changes that accompany breast cancer treatment, concerns about recurrence and mortality, and significant sexual and reproductive consequences of treatment that alters ovarian function. Pregnancy-associated breast cancers (breast cancers diagnosed during pregnancy, lactation, and for 12 months postpartum) represent a small subset of these cancers and occur in about 1 in 3,000 pregnancies. One might anticipate that this rate will increase as women continue to delay childbearing, because pregnancy-associated breast cancers are more common in older women.

In the review article by Howard-Anderson and colleagues, the importance of these reproductive health consequences in young women diagnosed with breast cancer is highlighted. The women who transition to menopause as a result of chemotherapy (reported to range from 33%–73%) experience more symptoms, including hot flashes, night sweats, breast pain, vaginal dryness, and lack of sexual desire. Sixty-one percent of women younger than 40 years at diagnosis reported that they were concerned about menopause, and 30% reported that this concern influenced their treatment decisions. Thirty-nine percent of women in this group had major concerns about treatment-associated infertility, and only half of the women studied felt that their fertility concerns were adequately addressed.

On a positive note, for women who successfully achieve pregnancy after breast cancer, pregnancy outcomes appear to be similar to those of their nonpregnant peers. In the study by Azim and colleagues, women who became pregnant after a breast cancer diagnosis had disease-free survival that was statistically similar to that of matched women who did not have subsequent pregnancies. In addition, this outcome did not differ based on estrogen/progesterone receptor status (ER/PR positive or negative).

We want to hear from you! Tell us what you think.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

[email protected]

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

[email protected]

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

SAN ANTONIO – Dietary restrictions prescribed for children with food allergies may lead to growth impairment, according to findings from a review of medical records for 245 food-allergic pediatric patients.

The risk of growth impairment was greatest for children whose dietary restrictions required elimination of more than two foods and/or elimination of cow’s milk, Dr. Brian P. Vickery reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

After age 2 years, the food-allergic children had lower mean percentiles for weight (67.5 vs. 72.5) and a lower body mass index (57.6 vs.68.0), than did 4,584 healthy age-matched controls.

Furthermore, the 52 patients with more than two food allergies (and thus more than two food restrictions), compared with 193 patients with one or two food allergies, had significantly lower mean percentiles for height (62.2 vs. 74.8) and weight (55.3 vs. 69.2). The 66 patients with milk allergy, compared with those with other food allergies, had lower mean percentiles for weight (54.5 vs. 70.6) and BMI (48.9 vs. 58.8), according to Dr. Vickery of the University of North Carolina at Chapel Hill.

Milk-allergic children younger than 2 years of age were particularly vulnerable to growth restriction, he said during a press briefing at the meeting.

The food-allergic children in this study, who were aged 1 month to 11 years and who presented to a University of North Carolina outpatient clinic between 2007 and 2011, also were compared with 205 "disease controls," consisting of children with either cystic fibrosis or celiac disease, two conditions that are associated with impaired growth. When children passed their second birthday, the effect of food allergy on growth was very similar to the effect of celiac disease on growth, Dr. Vickery said.

The findings of this study confirm those from a smaller study, conducted more than a decade ago, that also showed that milk allergy and multiple food allergies were associated with growth impairment.

That study is "the most commonly cited previous study to address the growth of food-allergic children in the United States," Dr. Vickery noted.

"The prevalence [of food allergy] has increased over the past 10 years, so we wanted to take another look in a bigger population to kind of reassess the impact of elimination diets on growth," he said.

The current findings demonstrate that a food allergy–associated elimination diet can place children at risk of impaired growth, compared with their healthy peers, regardless of whether they are under age 2 years, or are 2-11 years old, and that after age 2, the effect of food allergy on growth is very similar to that of chronic diseases known to affect growth, he said.

"While awareness of food allergy is increasing along with the prevalence of the disease, it is important to draw attention to the important consequences of elimination diets. We feel that providers should counsel patients and caregivers about the growth-related risks of the elimination diets that are used to treat food allergy, and ensure that families are excluding only the foods that are medically required or otherwise culturally indicated, that nutritional assessment and/or supplementation is provided as needed, and that subspecialty consultation is arranged, especially for children at highest risk," he said.

Dr. Vickery reported having no relevant financial disclosures.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

[email protected]

Episodic heavy drinking, like alcoholism and drug addiction, is increasingly recognized as a medical problem that primary care physicians can, and should, address.¹ But it is rarely the chief reason for an office visit. Nor is it a subject patients are likely to bring up.

However, patients are generally willing to talk to a trusted doctor who asks about their use (or misuse) of alcohol or other substances. And primary care physicians can do much to help—with brief interventions, a growing armamentarium of pharmacotherapy, and referrals as needed. In the pages that follow, you’ll find easy-to-use screening tools and effective intervention strategies.

SCREENING NEEDN'T BE TIME-CONSUMING

Screening for substance use isn’t difficult. In fact, it can usually be accomplished with 2 targeted questions—one for alcohol use and one for drugs.

Alcohol. Two single-question screens to detect hazardous drinking have been validated, despite having different parameters. Ask either:

Q: When was the last time you had more than ____ drinks (4 for women and 5 for men) in one day?

Q: How many times in the past year have you had ___ or more drinks (4 for women and 5 for men) in one day?

For the first question, any answer within the past 3 months is a positive screen for hazardous drinking.² For the second, anything other than zero is positive.^3,4

Initial screening can also be done with the AUDIT-C (TABLE), a validated short (3-question) version of the Alcohol Use Disorders Identification Test that can be self-administered.^5,6

Drugs. Only one single-question screen for drug use has been validated:

Q: How many times in the past year have you used an illegal drug or taken a prescription medication for nonmedical reasons?

Any answer other than never is a positive screen for hazardous drug use.⁷

CASE Jason F, a healthy and fit 28-year-old, has been your patient, along with his family, for years. He’s in your office because of a knee injury he incurred while running, and you take a moment to ask him, for the first time, how much he drinks and whether he takes drugs. His answer—that he drinks 3 or 4 times a week and often has multiple drinks at parties or nights out with the guys—takes you a bit by surprise.

Now what?

Watch the video

TABLE

3-question AUDIT-C screen for alcohol dependence^5,6

TELL ME MORE ABOUT IT

It is important to respond to a positive screen by requesting more information. In the conversation that ensues, the patient may provide the details you need to determine whether the drinking or drug use is indicative of a diagnosable substance use disorder, an umbrella term for alcohol or drug abuse and alcohol or drug dependence.

Alcohol or drug abuse vs dependence. Criteria for alcohol or drug abuse in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision (DSM-IV-TR) include risky behavior, such as drinking and driving; problems with work and/or close relationships; or run-ins with the law, such as an arrest for driving while intoxicated. Criteria for alcohol or drug dependence include the inability to cut down or stop using the substance; evidence of tolerance and withdrawal; spending more time ingesting the substance; increasing attention to substance use while interest in other activities diminishes; and continued use despite recurrent problems.⁸

Tools zero in on extent of problem

To learn more about your patient’s situation, consider using the following criteria and tools:

DSM criteria. Ask the following 2 questions, which are among DSM-IV-TR criteria for alcohol dependence:

1. How many times in the last year have you had a lot more to drink than you intended?
2. How many times in the last year have you been drinking in situations where it could have been hazardous, where you could have caused an accident or gotten hurt?

Any answer other than zero to either question is suggestive of a substance use disorder. In exploratory analyses, this approach had positive likelihood ratios of 4.7 to 16 and negative likelihood ratios of 0.05 to 0.30.^9,10

Although the above questions refer to alcohol use, they could be revised to learn more about a patient’s use of marijuana or other drugs, as well. (There are few tools for the assessment of drug use, because any illegal or nonmedical use of controlled substances has clear risks of major harm.)

CAGE. Another tool that is effective in assessing alcohol use is the 4-question CAGE—an acronym for Cut down, Annoyed, Guilty, and Eye opener:

• Have you ever felt that you should cut down on your drinking?
• Have people annoyed you by criticizing your drinking?
• Have you ever felt bad or guilty about your drinking?
• Have you ever had a drink in the morning to get rid of a hangover?

One meta-analysis found that a positive CAGE test—ie, a positive response to one or more of the questions—had a sensitivity of 0.85 and a specificity of 0.78 in identifying alcohol dependence in a primary care setting (using DSM criteria as the gold standard).¹¹

AUDIT. This 10-item tool, a longer version of the AUDIT-C (available at http://www.medstudentlearning.com/node/6556), can also be used to determine the extent of alcohol use. This test provides detailed information about the quantity and frequency of alcohol use; however, it does not clearly distinguish between hazardous drinking and alcohol use disorders.¹²

If the patient is a teen

Assessment methods can be adjusted without difficulty to fit the age of the patient. The National Institute on Alcohol Abuse and Alcoholism has published the Alcohol Screening and Brief Intervention for Youth: A Practitioner’s Guide, available at http://www.niaaa.nih.gov/Publications/EducationTrainingMaterials/Pages/YouthGuide.aspx. The 6-question CRAFFT (for Car, Relax, Alone, Forget, Friends, Trouble) is a validated tool designed to assess adolescents’ use of both alcohol and drugs (http://www.ceasar-boston.org/clinicians/crafft.php).^13,14

CASE You give Mr. F the CAGE test, and he answers No to all 4 questions. You conclude that while his drinking may be hazardous, he does not appear to have alcohol abuse or dependence.

FOLLOW UP WITH A BRIEF INTERVENTION

For decades, evidence has shown that brief interventions are often effective in helping hazardous drinkers like Mr. F cut back to safer levels.^15-18 In some cases, the impact has been great enough to reduce health care and societal costs for up to 4 years¹⁹ and to cut the risk of alcohol-related death by about half.²⁰ As a result, the US Preventive Services Task Force has given a B rating to counseling to reduce alcohol misuse by primary care providers.²¹ (There is less evidence that brief interventions are effective for drug problems,²² or in settings other than primary care.²³)

Treat drug/alcohol problems

If you determine that your patient is engaging in hazardous alcohol or drug use or has a diagnosable substance use disorder, you do not have to drop everything else or treat it as an acute event. What matters is long-term success, which is best achieved by partnering with the patient.

Start by approaching drug and alcohol problems as you would a case of newly elevated blood pressure. Bring up the problem, seeking to engage the patient in addres- sing it.

If he or she does not agree to quit or cut back on drinking the first time you broach the subject, don’t be surprised or discouraged. Keep in mind that patients do not always respond positively to advice about handling chronic medical conditions either, particularly at first, and that you’ll be working together over time. What’s important, in the jargon of the Stages of Change model,²⁴ is to help the patient move from precontemplation to contemplation, and perhaps beyond that to planning or action.

Use motivational interviewing to partner with patients

Motivational interviewing is useful in helping patients change health-related behaviors. The technique, which is not hard to learn or apply, is based on the recognition that a simple shift in style toward a guiding (rather than directive) approach can often reap benefits that are immediately apparent. ^25-28

Motivational Interviewing: Helping People Change (3rd ed, by William R. Miller and Stephen Rollnick; Guilford Press, 2013) is an excellent resource for clinicians who wish to master this technique. An online tutorial in screening and brief intervention for alcohol or drug misuse is available free at https://adept.missouri.edu. Video demonstrations of motivational interviewing to address these issues are also available here ; to access them, click on “Training”, then on “Go to SBIRT videos”).

CASE Before Mr. F’s visit is concluded, you initiate a conversation about alcohol use, stating: “As your doctor, I’m concerned that the amount of alcohol you’re drinking could be hazardous to your health. I recommend that you cut down to no more than 4 drinks in any one day and to no more than 14 drinks a week.” You make it clear that change is up to him, and ask what he thinks about what you’ve said.

You also schedule a return visit in one month, at which time you will continue the conversation.

PHARMACOTHERAPY IS A USEFUL TOOL

Increasingly, alcohol and drug dependence—like other chronic conditions—can be effectively addressed with medication.

Drugs to treat alcohol dependence

Naltrexone. A daily dose of naltrexone, starting at 25 mg daily for a few days and going as high as 100 mg/d, can help patients with alcohol dependence limit their drinking to safe levels (number needed to treat [NNT]=9).²⁹ This will reduce the risk of alcohol-related harm while the patient considers quitting.

The most common adverse effect is nausea, but a low starting dose may alleviate it. Naltrexone, also available as a 380-mg intramuscular (IM) depot injection once every 4 weeks, is an opioid antagonist and should not be given to any patient who’s taking opioids.

A 2010 Cochrane review found only 4 trials of naltrexone IM, and failed to show significant reductions in drinking.²⁹ But post hoc analyses of trials of both oral and IM naltrexone found that those in which compliance was assured (either by direct observation or IM administration) had better outcomes than those in which it was not.³⁰ Another post hoc analysis found that patients whose alcohol dependence was more severe derived greater benefits from the drug than those who were less severely affected.³¹

Acamprosate. Two 333-mg pills tid can help newly abstinent drinkers remain alcohol-free (NNT=9).^32,33 The most common adverse effect is diarrhea, which may subside with continued use.

Combining acamprosate and naltrexone does not appear to be more effective than either drug alone. In a recently published meta-analysis comparing the 2 drugs, those taking acamprosate had slightly better rates of abstinence from alcohol, while naltrexone was slightly better in reducing heavy drinking.³⁴

Disulfiram Unlike naltrexone and acamprosate, which work by altering the brain’s reward circuits, disulfiram blocks metabolism of ethanol, leading to the accumulation of a toxic metabolite and its punishing syndrome. The major problem with the drug is noncompliance, which can be addressed by enlisting the help of a caregiver or partner to ensure that it is taken daily. ^35-37

Other medications that have been tested (though not approved by the US Food and Drug Administration [FDA]) as a treatment for alcohol dependence include:

• topiramate, which has been found to have modest efficacy in increasing the number of abstinent days and decreasing heavy-drinking days;³⁸
• baclofen, which has shown efficacy in small clinical trials;³⁹ and
• ondansetron, which has been shown to effectively treat early-onset alcohol dependence.^40,41

For patients with depression and alcohol dependence, the combination of naltrexone and sertraline has been found to be superior to either drug by itself—and to have fewer adverse effects. ⁴² Gabapentin and lorazepam have been compared in treating alcohol withdrawal, with gabapentin resulting in greater efficacy and fewer adverse effects than lorazepam.^43,44

Pharmacotherapy for drug abuse, dependence

For methamphetamine abuse and dependence. Two randomized clinical trials have studied medications for methamphetamine abuse and dependence. In one small study, topiramate did not increase the proportion of patients who achieved abstinence, but in a post hoc subgroup analysis, it did appear to help newly abstinent patients avoid relapse.⁴⁵

In another study, mirtazapine significantly decreased the proportion of patients whose weekly urine tests were positive for methamphetamine (from 73% to 44%); no significant change was found among those on placebo.⁴⁶

Both drugs were well tolerated, but compliance was low in both trials despite weekly counseling. Each has only one clinical trial to support its use, and neither has FDA approval for addiction treatment.

For marijuana dependence. In a study of 50 people seeking treatment for marijuana dependence, gabapentin 400 mg 3 times a day significantly improved the proportion reporting no cannabis use and whose urine tested negative for the drug.⁴⁷

Another recent trial randomized adolescents dependent on cannabis to placebo or N-acetylcysteine 1200 mg twice a day. Those on the active drug were 2.4 times more likely than those on placebo to have negative urine tests with a number needed to treat of 7.⁴⁸ Both trials ran for about 3 months. Neither drug is FDA approved to treat marijuana dependence.

For opioid dependence. As maintenance medication for patients dependent on opioids, both methadone and buprenorphine have been shown to reduce the use of illicit opioids, lower mortality, and improve retention compared with treatment without medication.⁴⁹ Methadone would be a better choice than buprenorphine, which is a partial agonist with a ceiling on both its good (eg, stopping craving) and bad (eg, overdose risk) effects. In an open-label observational study of patients’ preferences, those who chose methadone maintenance over buprenorphine were twice as likely to remain in treatment.⁵⁰ Both drugs are FDA-approved for treating opioid dependence.

Methadone is a full agonist that can be given for opioid dependence only in a federally licensed methadone maintenance clinic. It has been shown to reduce the use of other opioids, reduce criminal behaviors,⁵¹ improve function in many areas,⁵² and reduce mortality.⁵³ In a cohort study of Massachusetts Medicaid data, methadone reduced mortality, which was 75% higher among those receiving abstinence-based treatment.^52,54

Buprenorphine (alone and in combination with naloxone), effectively reduces the use of illicit opioids and improves functional status.^55-57

Naltrexone, an opioid antagonist, may be effective in the treatment of opioid dependence. As with disulfiram for alcohol dependence, a major limitation of naltrexone for opioid dependence is noncompliance. But once a patient has been on oral naltrexone, he or she can be switched to naltrexone IM, which can be administered every 4 weeks. A Cochrane review published in 2011 found no evidence that naltrexone was superior to placebo, ⁵⁸ but since then another randomized clinical trial has been published that found naltrexone 380 mg IM every 4 weeks was superior to IM placebo. Patients on naltrexone were more likely to remain in treatment and have opioid-free urine tests, and reported less craving for opioids.⁵⁹ Both oral and depot injection naltrexone are FDA approved for treatment of opioid dependence. No comparisons of naltrexone vs either methadone or buprenorphine have been published.

To learn more about pharmacotherapy for opioid dependence, see “Diagnosing and treating opioid dependence” (J Fam Pract. 2012;61:588-596).

DEALING WITH THE CHALLENGES

As noted earlier, some patients with substance use disorders, like some patients with depression or hypertension, respond well to care and counseling, and some do not. Just as with other conditions, consultation with a specialist often helps.

A major difference in arranging consultations for patients with substance use disorders, however, is that clinicians who specialize in substance abuse and dependence often work in health care systems that are largely, or entirely, separate from those in which primary care physicians typically work. This, plus the stigma that surrounds problems with substance use, presents barriers to patients, who may shy away from going across town or to another city to see a provider they don’t know for a problem they’re either resistant to “owning” or ashamed of.

Yet it is possible to reach across this divide and make it easier for patients. One way to do that might be to partner with a local alcohol- and drug-treatment program so that your patients are referred, not to a faceless agency, but rather to a specific clinician; you might even call the provider while the patient is in your office so they can “meet.” Another approach, taken by some multispecialty practices, is to add psychotherapists to the staff so that patients can simply walk down the hall to obtain the mental health care they need.

Reaching across this divide is also a useful strategy for primary care physicians, who may welcome opportunities to meet with someone from a local treatment agency, not just for referrals but to learn more about treating patients with substance use problems. The Patient Protection and Affordable Care Act, which cites substance use disorders as one of 6 chronic health conditions that primary care medical homes are expected to address, may lead to better integration of health care systems that address physical health, as well as mental health and substance use disorders.

Episodic heavy drinking, like alcoholism and drug addiction, is increasingly recognized as a medical problem that primary care physicians can, and should, address.¹ But it is rarely the chief reason for an office visit. Nor is it a subject patients are likely to bring up.

However, patients are generally willing to talk to a trusted doctor who asks about their use (or misuse) of alcohol or other substances. And primary care physicians can do much to help—with brief interventions, a growing armamentarium of pharmacotherapy, and referrals as needed. In the pages that follow, you’ll find easy-to-use screening tools and effective intervention strategies.

SCREENING NEEDN'T BE TIME-CONSUMING

Screening for substance use isn’t difficult. In fact, it can usually be accomplished with 2 targeted questions—one for alcohol use and one for drugs.

Alcohol. Two single-question screens to detect hazardous drinking have been validated, despite having different parameters. Ask either:

Q: When was the last time you had more than ____ drinks (4 for women and 5 for men) in one day?

Q: How many times in the past year have you had ___ or more drinks (4 for women and 5 for men) in one day?

For the first question, any answer within the past 3 months is a positive screen for hazardous drinking.² For the second, anything other than zero is positive.^3,4

Initial screening can also be done with the AUDIT-C (TABLE), a validated short (3-question) version of the Alcohol Use Disorders Identification Test that can be self-administered.^5,6

Drugs. Only one single-question screen for drug use has been validated:

Q: How many times in the past year have you used an illegal drug or taken a prescription medication for nonmedical reasons?

Any answer other than never is a positive screen for hazardous drug use.⁷

CASE Jason F, a healthy and fit 28-year-old, has been your patient, along with his family, for years. He’s in your office because of a knee injury he incurred while running, and you take a moment to ask him, for the first time, how much he drinks and whether he takes drugs. His answer—that he drinks 3 or 4 times a week and often has multiple drinks at parties or nights out with the guys—takes you a bit by surprise.

Now what?

Watch the video

TABLE

3-question AUDIT-C screen for alcohol dependence^5,6

TELL ME MORE ABOUT IT

It is important to respond to a positive screen by requesting more information. In the conversation that ensues, the patient may provide the details you need to determine whether the drinking or drug use is indicative of a diagnosable substance use disorder, an umbrella term for alcohol or drug abuse and alcohol or drug dependence.

Alcohol or drug abuse vs dependence. Criteria for alcohol or drug abuse in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision (DSM-IV-TR) include risky behavior, such as drinking and driving; problems with work and/or close relationships; or run-ins with the law, such as an arrest for driving while intoxicated. Criteria for alcohol or drug dependence include the inability to cut down or stop using the substance; evidence of tolerance and withdrawal; spending more time ingesting the substance; increasing attention to substance use while interest in other activities diminishes; and continued use despite recurrent problems.⁸

Tools zero in on extent of problem

To learn more about your patient’s situation, consider using the following criteria and tools:

DSM criteria. Ask the following 2 questions, which are among DSM-IV-TR criteria for alcohol dependence:

1. How many times in the last year have you had a lot more to drink than you intended?
2. How many times in the last year have you been drinking in situations where it could have been hazardous, where you could have caused an accident or gotten hurt?

Any answer other than zero to either question is suggestive of a substance use disorder. In exploratory analyses, this approach had positive likelihood ratios of 4.7 to 16 and negative likelihood ratios of 0.05 to 0.30.^9,10

Although the above questions refer to alcohol use, they could be revised to learn more about a patient’s use of marijuana or other drugs, as well. (There are few tools for the assessment of drug use, because any illegal or nonmedical use of controlled substances has clear risks of major harm.)

CAGE. Another tool that is effective in assessing alcohol use is the 4-question CAGE—an acronym for Cut down, Annoyed, Guilty, and Eye opener:

• Have you ever felt that you should cut down on your drinking?
• Have people annoyed you by criticizing your drinking?
• Have you ever felt bad or guilty about your drinking?
• Have you ever had a drink in the morning to get rid of a hangover?

One meta-analysis found that a positive CAGE test—ie, a positive response to one or more of the questions—had a sensitivity of 0.85 and a specificity of 0.78 in identifying alcohol dependence in a primary care setting (using DSM criteria as the gold standard).¹¹

AUDIT. This 10-item tool, a longer version of the AUDIT-C (available at http://www.medstudentlearning.com/node/6556), can also be used to determine the extent of alcohol use. This test provides detailed information about the quantity and frequency of alcohol use; however, it does not clearly distinguish between hazardous drinking and alcohol use disorders.¹²

If the patient is a teen

Assessment methods can be adjusted without difficulty to fit the age of the patient. The National Institute on Alcohol Abuse and Alcoholism has published the Alcohol Screening and Brief Intervention for Youth: A Practitioner’s Guide, available at http://www.niaaa.nih.gov/Publications/EducationTrainingMaterials/Pages/YouthGuide.aspx. The 6-question CRAFFT (for Car, Relax, Alone, Forget, Friends, Trouble) is a validated tool designed to assess adolescents’ use of both alcohol and drugs (http://www.ceasar-boston.org/clinicians/crafft.php).^13,14

CASE You give Mr. F the CAGE test, and he answers No to all 4 questions. You conclude that while his drinking may be hazardous, he does not appear to have alcohol abuse or dependence.

FOLLOW UP WITH A BRIEF INTERVENTION

For decades, evidence has shown that brief interventions are often effective in helping hazardous drinkers like Mr. F cut back to safer levels.^15-18 In some cases, the impact has been great enough to reduce health care and societal costs for up to 4 years¹⁹ and to cut the risk of alcohol-related death by about half.²⁰ As a result, the US Preventive Services Task Force has given a B rating to counseling to reduce alcohol misuse by primary care providers.²¹ (There is less evidence that brief interventions are effective for drug problems,²² or in settings other than primary care.²³)

Treat drug/alcohol problems

If you determine that your patient is engaging in hazardous alcohol or drug use or has a diagnosable substance use disorder, you do not have to drop everything else or treat it as an acute event. What matters is long-term success, which is best achieved by partnering with the patient.

Start by approaching drug and alcohol problems as you would a case of newly elevated blood pressure. Bring up the problem, seeking to engage the patient in addres- sing it.

If he or she does not agree to quit or cut back on drinking the first time you broach the subject, don’t be surprised or discouraged. Keep in mind that patients do not always respond positively to advice about handling chronic medical conditions either, particularly at first, and that you’ll be working together over time. What’s important, in the jargon of the Stages of Change model,²⁴ is to help the patient move from precontemplation to contemplation, and perhaps beyond that to planning or action.

Use motivational interviewing to partner with patients

Motivational interviewing is useful in helping patients change health-related behaviors. The technique, which is not hard to learn or apply, is based on the recognition that a simple shift in style toward a guiding (rather than directive) approach can often reap benefits that are immediately apparent. ^25-28

Motivational Interviewing: Helping People Change (3rd ed, by William R. Miller and Stephen Rollnick; Guilford Press, 2013) is an excellent resource for clinicians who wish to master this technique. An online tutorial in screening and brief intervention for alcohol or drug misuse is available free at https://adept.missouri.edu. Video demonstrations of motivational interviewing to address these issues are also available here ; to access them, click on “Training”, then on “Go to SBIRT videos”).

CASE Before Mr. F’s visit is concluded, you initiate a conversation about alcohol use, stating: “As your doctor, I’m concerned that the amount of alcohol you’re drinking could be hazardous to your health. I recommend that you cut down to no more than 4 drinks in any one day and to no more than 14 drinks a week.” You make it clear that change is up to him, and ask what he thinks about what you’ve said.

You also schedule a return visit in one month, at which time you will continue the conversation.

PHARMACOTHERAPY IS A USEFUL TOOL

Increasingly, alcohol and drug dependence—like other chronic conditions—can be effectively addressed with medication.

Drugs to treat alcohol dependence

Naltrexone. A daily dose of naltrexone, starting at 25 mg daily for a few days and going as high as 100 mg/d, can help patients with alcohol dependence limit their drinking to safe levels (number needed to treat [NNT]=9).²⁹ This will reduce the risk of alcohol-related harm while the patient considers quitting.

The most common adverse effect is nausea, but a low starting dose may alleviate it. Naltrexone, also available as a 380-mg intramuscular (IM) depot injection once every 4 weeks, is an opioid antagonist and should not be given to any patient who’s taking opioids.

A 2010 Cochrane review found only 4 trials of naltrexone IM, and failed to show significant reductions in drinking.²⁹ But post hoc analyses of trials of both oral and IM naltrexone found that those in which compliance was assured (either by direct observation or IM administration) had better outcomes than those in which it was not.³⁰ Another post hoc analysis found that patients whose alcohol dependence was more severe derived greater benefits from the drug than those who were less severely affected.³¹

Acamprosate. Two 333-mg pills tid can help newly abstinent drinkers remain alcohol-free (NNT=9).^32,33 The most common adverse effect is diarrhea, which may subside with continued use.

Combining acamprosate and naltrexone does not appear to be more effective than either drug alone. In a recently published meta-analysis comparing the 2 drugs, those taking acamprosate had slightly better rates of abstinence from alcohol, while naltrexone was slightly better in reducing heavy drinking.³⁴

Disulfiram Unlike naltrexone and acamprosate, which work by altering the brain’s reward circuits, disulfiram blocks metabolism of ethanol, leading to the accumulation of a toxic metabolite and its punishing syndrome. The major problem with the drug is noncompliance, which can be addressed by enlisting the help of a caregiver or partner to ensure that it is taken daily. ^35-37

Other medications that have been tested (though not approved by the US Food and Drug Administration [FDA]) as a treatment for alcohol dependence include:

• topiramate, which has been found to have modest efficacy in increasing the number of abstinent days and decreasing heavy-drinking days;³⁸
• baclofen, which has shown efficacy in small clinical trials;³⁹ and
• ondansetron, which has been shown to effectively treat early-onset alcohol dependence.^40,41

For patients with depression and alcohol dependence, the combination of naltrexone and sertraline has been found to be superior to either drug by itself—and to have fewer adverse effects. ⁴² Gabapentin and lorazepam have been compared in treating alcohol withdrawal, with gabapentin resulting in greater efficacy and fewer adverse effects than lorazepam.^43,44

Pharmacotherapy for drug abuse, dependence

For methamphetamine abuse and dependence. Two randomized clinical trials have studied medications for methamphetamine abuse and dependence. In one small study, topiramate did not increase the proportion of patients who achieved abstinence, but in a post hoc subgroup analysis, it did appear to help newly abstinent patients avoid relapse.⁴⁵

In another study, mirtazapine significantly decreased the proportion of patients whose weekly urine tests were positive for methamphetamine (from 73% to 44%); no significant change was found among those on placebo.⁴⁶

Both drugs were well tolerated, but compliance was low in both trials despite weekly counseling. Each has only one clinical trial to support its use, and neither has FDA approval for addiction treatment.

For marijuana dependence. In a study of 50 people seeking treatment for marijuana dependence, gabapentin 400 mg 3 times a day significantly improved the proportion reporting no cannabis use and whose urine tested negative for the drug.⁴⁷

Another recent trial randomized adolescents dependent on cannabis to placebo or N-acetylcysteine 1200 mg twice a day. Those on the active drug were 2.4 times more likely than those on placebo to have negative urine tests with a number needed to treat of 7.⁴⁸ Both trials ran for about 3 months. Neither drug is FDA approved to treat marijuana dependence.

For opioid dependence. As maintenance medication for patients dependent on opioids, both methadone and buprenorphine have been shown to reduce the use of illicit opioids, lower mortality, and improve retention compared with treatment without medication.⁴⁹ Methadone would be a better choice than buprenorphine, which is a partial agonist with a ceiling on both its good (eg, stopping craving) and bad (eg, overdose risk) effects. In an open-label observational study of patients’ preferences, those who chose methadone maintenance over buprenorphine were twice as likely to remain in treatment.⁵⁰ Both drugs are FDA-approved for treating opioid dependence.

Methadone is a full agonist that can be given for opioid dependence only in a federally licensed methadone maintenance clinic. It has been shown to reduce the use of other opioids, reduce criminal behaviors,⁵¹ improve function in many areas,⁵² and reduce mortality.⁵³ In a cohort study of Massachusetts Medicaid data, methadone reduced mortality, which was 75% higher among those receiving abstinence-based treatment.^52,54

Buprenorphine (alone and in combination with naloxone), effectively reduces the use of illicit opioids and improves functional status.^55-57

Naltrexone, an opioid antagonist, may be effective in the treatment of opioid dependence. As with disulfiram for alcohol dependence, a major limitation of naltrexone for opioid dependence is noncompliance. But once a patient has been on oral naltrexone, he or she can be switched to naltrexone IM, which can be administered every 4 weeks. A Cochrane review published in 2011 found no evidence that naltrexone was superior to placebo, ⁵⁸ but since then another randomized clinical trial has been published that found naltrexone 380 mg IM every 4 weeks was superior to IM placebo. Patients on naltrexone were more likely to remain in treatment and have opioid-free urine tests, and reported less craving for opioids.⁵⁹ Both oral and depot injection naltrexone are FDA approved for treatment of opioid dependence. No comparisons of naltrexone vs either methadone or buprenorphine have been published.

To learn more about pharmacotherapy for opioid dependence, see “Diagnosing and treating opioid dependence” (J Fam Pract. 2012;61:588-596).

DEALING WITH THE CHALLENGES

As noted earlier, some patients with substance use disorders, like some patients with depression or hypertension, respond well to care and counseling, and some do not. Just as with other conditions, consultation with a specialist often helps.

A major difference in arranging consultations for patients with substance use disorders, however, is that clinicians who specialize in substance abuse and dependence often work in health care systems that are largely, or entirely, separate from those in which primary care physicians typically work. This, plus the stigma that surrounds problems with substance use, presents barriers to patients, who may shy away from going across town or to another city to see a provider they don’t know for a problem they’re either resistant to “owning” or ashamed of.

Yet it is possible to reach across this divide and make it easier for patients. One way to do that might be to partner with a local alcohol- and drug-treatment program so that your patients are referred, not to a faceless agency, but rather to a specific clinician; you might even call the provider while the patient is in your office so they can “meet.” Another approach, taken by some multispecialty practices, is to add psychotherapists to the staff so that patients can simply walk down the hall to obtain the mental health care they need.

Reaching across this divide is also a useful strategy for primary care physicians, who may welcome opportunities to meet with someone from a local treatment agency, not just for referrals but to learn more about treating patients with substance use problems. The Patient Protection and Affordable Care Act, which cites substance use disorders as one of 6 chronic health conditions that primary care medical homes are expected to address, may lead to better integration of health care systems that address physical health, as well as mental health and substance use disorders.

Episodic heavy drinking, like alcoholism and drug addiction, is increasingly recognized as a medical problem that primary care physicians can, and should, address.¹ But it is rarely the chief reason for an office visit. Nor is it a subject patients are likely to bring up.

However, patients are generally willing to talk to a trusted doctor who asks about their use (or misuse) of alcohol or other substances. And primary care physicians can do much to help—with brief interventions, a growing armamentarium of pharmacotherapy, and referrals as needed. In the pages that follow, you’ll find easy-to-use screening tools and effective intervention strategies.

SCREENING NEEDN'T BE TIME-CONSUMING

Screening for substance use isn’t difficult. In fact, it can usually be accomplished with 2 targeted questions—one for alcohol use and one for drugs.

Alcohol. Two single-question screens to detect hazardous drinking have been validated, despite having different parameters. Ask either:

Q: When was the last time you had more than ____ drinks (4 for women and 5 for men) in one day?

Q: How many times in the past year have you had ___ or more drinks (4 for women and 5 for men) in one day?

For the first question, any answer within the past 3 months is a positive screen for hazardous drinking.² For the second, anything other than zero is positive.^3,4

Initial screening can also be done with the AUDIT-C (TABLE), a validated short (3-question) version of the Alcohol Use Disorders Identification Test that can be self-administered.^5,6

Drugs. Only one single-question screen for drug use has been validated:

Q: How many times in the past year have you used an illegal drug or taken a prescription medication for nonmedical reasons?

Any answer other than never is a positive screen for hazardous drug use.⁷

CASE Jason F, a healthy and fit 28-year-old, has been your patient, along with his family, for years. He’s in your office because of a knee injury he incurred while running, and you take a moment to ask him, for the first time, how much he drinks and whether he takes drugs. His answer—that he drinks 3 or 4 times a week and often has multiple drinks at parties or nights out with the guys—takes you a bit by surprise.

Now what?

Watch the video

TABLE

3-question AUDIT-C screen for alcohol dependence^5,6

TELL ME MORE ABOUT IT

It is important to respond to a positive screen by requesting more information. In the conversation that ensues, the patient may provide the details you need to determine whether the drinking or drug use is indicative of a diagnosable substance use disorder, an umbrella term for alcohol or drug abuse and alcohol or drug dependence.

Alcohol or drug abuse vs dependence. Criteria for alcohol or drug abuse in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision (DSM-IV-TR) include risky behavior, such as drinking and driving; problems with work and/or close relationships; or run-ins with the law, such as an arrest for driving while intoxicated. Criteria for alcohol or drug dependence include the inability to cut down or stop using the substance; evidence of tolerance and withdrawal; spending more time ingesting the substance; increasing attention to substance use while interest in other activities diminishes; and continued use despite recurrent problems.⁸

Tools zero in on extent of problem

To learn more about your patient’s situation, consider using the following criteria and tools:

DSM criteria. Ask the following 2 questions, which are among DSM-IV-TR criteria for alcohol dependence:

1. How many times in the last year have you had a lot more to drink than you intended?
2. How many times in the last year have you been drinking in situations where it could have been hazardous, where you could have caused an accident or gotten hurt?

Any answer other than zero to either question is suggestive of a substance use disorder. In exploratory analyses, this approach had positive likelihood ratios of 4.7 to 16 and negative likelihood ratios of 0.05 to 0.30.^9,10

Although the above questions refer to alcohol use, they could be revised to learn more about a patient’s use of marijuana or other drugs, as well. (There are few tools for the assessment of drug use, because any illegal or nonmedical use of controlled substances has clear risks of major harm.)

CAGE. Another tool that is effective in assessing alcohol use is the 4-question CAGE—an acronym for Cut down, Annoyed, Guilty, and Eye opener:

• Have you ever felt that you should cut down on your drinking?
• Have people annoyed you by criticizing your drinking?
• Have you ever felt bad or guilty about your drinking?
• Have you ever had a drink in the morning to get rid of a hangover?

One meta-analysis found that a positive CAGE test—ie, a positive response to one or more of the questions—had a sensitivity of 0.85 and a specificity of 0.78 in identifying alcohol dependence in a primary care setting (using DSM criteria as the gold standard).¹¹

AUDIT. This 10-item tool, a longer version of the AUDIT-C (available at http://www.medstudentlearning.com/node/6556), can also be used to determine the extent of alcohol use. This test provides detailed information about the quantity and frequency of alcohol use; however, it does not clearly distinguish between hazardous drinking and alcohol use disorders.¹²

If the patient is a teen

Assessment methods can be adjusted without difficulty to fit the age of the patient. The National Institute on Alcohol Abuse and Alcoholism has published the Alcohol Screening and Brief Intervention for Youth: A Practitioner’s Guide, available at http://www.niaaa.nih.gov/Publications/EducationTrainingMaterials/Pages/YouthGuide.aspx. The 6-question CRAFFT (for Car, Relax, Alone, Forget, Friends, Trouble) is a validated tool designed to assess adolescents’ use of both alcohol and drugs (http://www.ceasar-boston.org/clinicians/crafft.php).^13,14

CASE You give Mr. F the CAGE test, and he answers No to all 4 questions. You conclude that while his drinking may be hazardous, he does not appear to have alcohol abuse or dependence.

FOLLOW UP WITH A BRIEF INTERVENTION

For decades, evidence has shown that brief interventions are often effective in helping hazardous drinkers like Mr. F cut back to safer levels.^15-18 In some cases, the impact has been great enough to reduce health care and societal costs for up to 4 years¹⁹ and to cut the risk of alcohol-related death by about half.²⁰ As a result, the US Preventive Services Task Force has given a B rating to counseling to reduce alcohol misuse by primary care providers.²¹ (There is less evidence that brief interventions are effective for drug problems,²² or in settings other than primary care.²³)

Treat drug/alcohol problems

If you determine that your patient is engaging in hazardous alcohol or drug use or has a diagnosable substance use disorder, you do not have to drop everything else or treat it as an acute event. What matters is long-term success, which is best achieved by partnering with the patient.

Start by approaching drug and alcohol problems as you would a case of newly elevated blood pressure. Bring up the problem, seeking to engage the patient in addres- sing it.

If he or she does not agree to quit or cut back on drinking the first time you broach the subject, don’t be surprised or discouraged. Keep in mind that patients do not always respond positively to advice about handling chronic medical conditions either, particularly at first, and that you’ll be working together over time. What’s important, in the jargon of the Stages of Change model,²⁴ is to help the patient move from precontemplation to contemplation, and perhaps beyond that to planning or action.

Use motivational interviewing to partner with patients

Motivational interviewing is useful in helping patients change health-related behaviors. The technique, which is not hard to learn or apply, is based on the recognition that a simple shift in style toward a guiding (rather than directive) approach can often reap benefits that are immediately apparent. ^25-28

Motivational Interviewing: Helping People Change (3rd ed, by William R. Miller and Stephen Rollnick; Guilford Press, 2013) is an excellent resource for clinicians who wish to master this technique. An online tutorial in screening and brief intervention for alcohol or drug misuse is available free at https://adept.missouri.edu. Video demonstrations of motivational interviewing to address these issues are also available here ; to access them, click on “Training”, then on “Go to SBIRT videos”).

CASE Before Mr. F’s visit is concluded, you initiate a conversation about alcohol use, stating: “As your doctor, I’m concerned that the amount of alcohol you’re drinking could be hazardous to your health. I recommend that you cut down to no more than 4 drinks in any one day and to no more than 14 drinks a week.” You make it clear that change is up to him, and ask what he thinks about what you’ve said.

You also schedule a return visit in one month, at which time you will continue the conversation.

PHARMACOTHERAPY IS A USEFUL TOOL

Increasingly, alcohol and drug dependence—like other chronic conditions—can be effectively addressed with medication.

Drugs to treat alcohol dependence

Naltrexone. A daily dose of naltrexone, starting at 25 mg daily for a few days and going as high as 100 mg/d, can help patients with alcohol dependence limit their drinking to safe levels (number needed to treat [NNT]=9).²⁹ This will reduce the risk of alcohol-related harm while the patient considers quitting.

The most common adverse effect is nausea, but a low starting dose may alleviate it. Naltrexone, also available as a 380-mg intramuscular (IM) depot injection once every 4 weeks, is an opioid antagonist and should not be given to any patient who’s taking opioids.

A 2010 Cochrane review found only 4 trials of naltrexone IM, and failed to show significant reductions in drinking.²⁹ But post hoc analyses of trials of both oral and IM naltrexone found that those in which compliance was assured (either by direct observation or IM administration) had better outcomes than those in which it was not.³⁰ Another post hoc analysis found that patients whose alcohol dependence was more severe derived greater benefits from the drug than those who were less severely affected.³¹

Acamprosate. Two 333-mg pills tid can help newly abstinent drinkers remain alcohol-free (NNT=9).^32,33 The most common adverse effect is diarrhea, which may subside with continued use.

Combining acamprosate and naltrexone does not appear to be more effective than either drug alone. In a recently published meta-analysis comparing the 2 drugs, those taking acamprosate had slightly better rates of abstinence from alcohol, while naltrexone was slightly better in reducing heavy drinking.³⁴

Disulfiram Unlike naltrexone and acamprosate, which work by altering the brain’s reward circuits, disulfiram blocks metabolism of ethanol, leading to the accumulation of a toxic metabolite and its punishing syndrome. The major problem with the drug is noncompliance, which can be addressed by enlisting the help of a caregiver or partner to ensure that it is taken daily. ^35-37

Other medications that have been tested (though not approved by the US Food and Drug Administration [FDA]) as a treatment for alcohol dependence include:

• topiramate, which has been found to have modest efficacy in increasing the number of abstinent days and decreasing heavy-drinking days;³⁸
• baclofen, which has shown efficacy in small clinical trials;³⁹ and
• ondansetron, which has been shown to effectively treat early-onset alcohol dependence.^40,41

For patients with depression and alcohol dependence, the combination of naltrexone and sertraline has been found to be superior to either drug by itself—and to have fewer adverse effects. ⁴² Gabapentin and lorazepam have been compared in treating alcohol withdrawal, with gabapentin resulting in greater efficacy and fewer adverse effects than lorazepam.^43,44

Pharmacotherapy for drug abuse, dependence

For methamphetamine abuse and dependence. Two randomized clinical trials have studied medications for methamphetamine abuse and dependence. In one small study, topiramate did not increase the proportion of patients who achieved abstinence, but in a post hoc subgroup analysis, it did appear to help newly abstinent patients avoid relapse.⁴⁵

In another study, mirtazapine significantly decreased the proportion of patients whose weekly urine tests were positive for methamphetamine (from 73% to 44%); no significant change was found among those on placebo.⁴⁶

Both drugs were well tolerated, but compliance was low in both trials despite weekly counseling. Each has only one clinical trial to support its use, and neither has FDA approval for addiction treatment.

For marijuana dependence. In a study of 50 people seeking treatment for marijuana dependence, gabapentin 400 mg 3 times a day significantly improved the proportion reporting no cannabis use and whose urine tested negative for the drug.⁴⁷

Another recent trial randomized adolescents dependent on cannabis to placebo or N-acetylcysteine 1200 mg twice a day. Those on the active drug were 2.4 times more likely than those on placebo to have negative urine tests with a number needed to treat of 7.⁴⁸ Both trials ran for about 3 months. Neither drug is FDA approved to treat marijuana dependence.

For opioid dependence. As maintenance medication for patients dependent on opioids, both methadone and buprenorphine have been shown to reduce the use of illicit opioids, lower mortality, and improve retention compared with treatment without medication.⁴⁹ Methadone would be a better choice than buprenorphine, which is a partial agonist with a ceiling on both its good (eg, stopping craving) and bad (eg, overdose risk) effects. In an open-label observational study of patients’ preferences, those who chose methadone maintenance over buprenorphine were twice as likely to remain in treatment.⁵⁰ Both drugs are FDA-approved for treating opioid dependence.

Methadone is a full agonist that can be given for opioid dependence only in a federally licensed methadone maintenance clinic. It has been shown to reduce the use of other opioids, reduce criminal behaviors,⁵¹ improve function in many areas,⁵² and reduce mortality.⁵³ In a cohort study of Massachusetts Medicaid data, methadone reduced mortality, which was 75% higher among those receiving abstinence-based treatment.^52,54

Buprenorphine (alone and in combination with naloxone), effectively reduces the use of illicit opioids and improves functional status.^55-57

Naltrexone, an opioid antagonist, may be effective in the treatment of opioid dependence. As with disulfiram for alcohol dependence, a major limitation of naltrexone for opioid dependence is noncompliance. But once a patient has been on oral naltrexone, he or she can be switched to naltrexone IM, which can be administered every 4 weeks. A Cochrane review published in 2011 found no evidence that naltrexone was superior to placebo, ⁵⁸ but since then another randomized clinical trial has been published that found naltrexone 380 mg IM every 4 weeks was superior to IM placebo. Patients on naltrexone were more likely to remain in treatment and have opioid-free urine tests, and reported less craving for opioids.⁵⁹ Both oral and depot injection naltrexone are FDA approved for treatment of opioid dependence. No comparisons of naltrexone vs either methadone or buprenorphine have been published.

To learn more about pharmacotherapy for opioid dependence, see “Diagnosing and treating opioid dependence” (J Fam Pract. 2012;61:588-596).

DEALING WITH THE CHALLENGES

As noted earlier, some patients with substance use disorders, like some patients with depression or hypertension, respond well to care and counseling, and some do not. Just as with other conditions, consultation with a specialist often helps.

A major difference in arranging consultations for patients with substance use disorders, however, is that clinicians who specialize in substance abuse and dependence often work in health care systems that are largely, or entirely, separate from those in which primary care physicians typically work. This, plus the stigma that surrounds problems with substance use, presents barriers to patients, who may shy away from going across town or to another city to see a provider they don’t know for a problem they’re either resistant to “owning” or ashamed of.

Yet it is possible to reach across this divide and make it easier for patients. One way to do that might be to partner with a local alcohol- and drug-treatment program so that your patients are referred, not to a faceless agency, but rather to a specific clinician; you might even call the provider while the patient is in your office so they can “meet.” Another approach, taken by some multispecialty practices, is to add psychotherapists to the staff so that patients can simply walk down the hall to obtain the mental health care they need.

Reaching across this divide is also a useful strategy for primary care physicians, who may welcome opportunities to meet with someone from a local treatment agency, not just for referrals but to learn more about treating patients with substance use problems. The Patient Protection and Affordable Care Act, which cites substance use disorders as one of 6 chronic health conditions that primary care medical homes are expected to address, may lead to better integration of health care systems that address physical health, as well as mental health and substance use disorders.

Nearly 26 million US adults are estimated to have type 2 diabetes, including at least eight million who are unaware they have the disease.¹ An additional 80 million adults are affected by prediabetes, with above-average glucose levels that do not yet meet American Diabetes Association (ADA) criteria for type 2 diabetes.^1,2

In this context, the primary care provider is likely to encounter patients with a diagnosis of type 2 diabetes in its early stages. Which patients can be considered candidates for conservative management—that is, lifestyle modification—before antidiabetic medications are initiated?

Case Patient
A black woman, age 44, presented for a routine physical examination. She said she had been in good health until three months earlier, when she began to experience weakness and fatigue. She complained of increased thirst and frequent urination, requiring her to get up three or four times each night. She had increased her average fluid intake to nine glasses a day from the usual four. Despite a good appetite, she had lost about 7 lb over the previous three months.

The patient’s previous medical history was significant for four cesarean deliveries, gestational diabetes during all four pregnancies, hemorrhoids, constipation, keloid formation, and hyperlipidemia. Her family history was significant for diabetes (paternal side) and hyperlipidemia.

Findings from the patient’s physical exam included weight, 217 lb; height, 5’11”; BMI, 30.3; pulse, 80 beats/min and regular; and blood pressure, 138/78 mm Hg. With the exception of obesity and elevated systolic blood pressure, her physical exam findings were within normal limits.

Laboratory testing yielded the following results: urinalysis, 3+ glucose, negative for ketones and protein; fasting blood glucose, 145 mg/dL; hemoglobin A1C, 6.9%; total cholesterol, 230 mg/dL; HDL cholesterol (HDL-C), 21 mg/dL; LDL cholesterol (LDL-C), 144 mg/dL; and triglycerides, 400 mg/dL.

The patient’s history of gestational diabetes, her acknowledged sedentary lifestyle, body weight currently exceeding her ideal weight by 50 lb, and family history positive for diabetes put her at increased risk for diabetes. Also of concern was her elevated systolic blood pressure.

The patient’s A1C of 6.9% indicated that during the previous two months, her average blood glucose had been in excess of 125 mg/dL. A diagnosis of type 2 diabetes was made, based on the patient’s elevated fasting blood glucose and A1C, and the aforementioned symptoms of weight loss, fatigue, polydypsia, and polyuria. 

Because the patient was perceived as self-reliant and responsible, it was recommended that she be treated conservatively with a broad lifestyle modification regimen. Goals were to reduce all of her diabetes indicators, including weight,^3,4 blood pressure,⁵ and A1C, with an improved lipids profile—all, if possible, without the use of medication. The regimen comprised a low–glycemic index (GI) diet^6,7 to reduce her glucose level, and aerobic exercise and strength training⁸ to improve her cardiovascular health. With resulting weight loss and reduced salt intake,^3-5 it was expected that the patient would see reductions in her total cholesterol, LDL-C, and systolic blood pressure.

The patient’s management team recommended a daily plan of four small meals and one or two small snacks. She was advised to control portions by visually dividing her plate: Non-starchy (low-GI) vegetables should fill half of the plate, with the remaining half divided into equal sections for a small serving of protein and a small serving of carbohydrates with a GI of 55 or less (see figure^7,9).

Her exercise program was based on recommendations from the American Association of Clinical Endocrinologists (AACE)¹⁰ and the US Department of Health and Human Services¹¹: cardiovascular/aerobic exercise (five 30-minute sessions per week), ranging in intensity from moderate (eg, brisk walking, bicycling, doubles tennis) to vigorous (jogging or running, swimming laps, singles tennis); and strength training (two 30-minute sessions per week), such as weight-lifting, push-ups, and sit-ups.

Discussion
Type 2 diabetes mellitus affects an estimated 25.8 million residents of the United States, including an estimated 8.3 million who have not yet been diagnosed.¹ According to the CDC,¹² prevalence of diabetes is greatest in black and Hispanic women and men.

The sixth leading cause of death in the US, diabetes is also the leading cause of blindness (ie, diabetic retinopathy), kidney disease requiring dialysis, and lower-limb amputation. Diabetes is closely associated with cardiovascular disease (CVD), the leading cause of death in the US.¹² Other diabetes-related health concerns include hypertension, peripheral diabetic neuropathy, dental disease, depression, delayed wound healing, and increased risk for infection.¹²

The standard criteria for a diagnosis of diabetes, according to the 2012 ADA Standards of Medical Care in Diabetes,¹³ are:

• A1C exceeding 6.5%, or
• A fasting blood glucose level at or exceeding 126 mg/dL, or

• A 2-hour plasma glucose at or exceeding 200 mg/dL during an oral glucose tolerance test, or

• A random blood glucose of 200 mg/dL or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis.¹³

Treatment Goals
Goals for diabetic patients advocated by the National Diabetes Education Program (NDEP)¹ include maintaining blood pressure below 130/80 mm Hg, lowering LDL-C to below 100 mg/dL (and below 70 mg/dL in patients at risk for CVD), reducing triglyceride levels to below 150 mg/dL, and raising HDL-C above 40 mg/dL in women and above 50 mg/dL in men. Achieving these levels can reduce the diabetic patient’s risk for CVD and microvascular complications by 50%.¹

Medical Nutrition Therapy
The NDEP and other entities^1,14 refer to medical nutrition therapy as an integral component of diabetic management. This individualized meal plan, developed by a registered dietitian, is based on the patient’s nutritional status and preferences. To optimize the case patient’s glycemic control,¹⁰ a low-GI diet was selected.

As the ADA⁹ and Solomon et al¹⁵ have explained, this diet is based on foods that produce a reduced glucose response during the two hours after consumption. According to one literature review,¹⁶ use of a low-GI diet led a reduction in A1C of 0.43 percentage points. When combined with appropriate exercise, the low-GI diet can alleviate hypertension and postprandial hyperinsulinemia,^15,17 as well as levels of C-reactive protein, an inflammatory marker that in high concentrations is associated with increased risk for CVD.¹⁸

The Role of Exercise
The ADA 2012 standards¹³ recommend a minimum of 150 minutes per week of moderate physical activity. The benefits of exercise in diabetic patients include improved control of blood glucose and reduction of risk for heart disease and other illnesses.^3,11 Patients should be under the care of a provider who can help develop an appropriate, individualized plan.^3,11

According to ADA recommendations,¹³ the patient’s lipid levels, blood pressure, and smoking status should be evaluated, with assessment for the presence of CVD in at-risk patients. For asymptomatic diabetic patients, the American College of Cardiology/American Heart Association recommend an ECG stress test before an exercise program is undertaken.^19,20 Exercise is contraindicated in those with decompensated congestive heart failure, complex ventricular arrhythmias, unstable angina, significant aortic stenosis, or aortic aneurysm.¹⁹

Because initiating an exercise program incurs a slight risk for injury, patients should start gradually, warming up before each session and cooling down afterward.^11,19 Diabetic patients should also wear proper shoes for maximum foot protection. They must also be instructed to watch for signs of hypoglycemia during physical activity and be prepared to treat it.^11,13

Patient Outcome
After one year on her prescribed treatment regimen, the patient’s A1C was measured at 6.3%, and her LDL-C was 124 mg/dL. Another year later, her A1C was further reduced to 5.9%, and her LDL-C to 77.2 mg/dL. By then, she had lost 15 lb (BMI, 28.2) and perceived her current maintenance plan as enjoyable and manageable, long-term: She was exercising every day possible, with seven sessions of at least 30 minutes, and maintaining a diet of low-GI foods. The patient was committed to following up with her clinician for glucose monitoring every three months.

Conclusion
As illustrated in this patient’s case, the best plan for management of diabetes in its early stages is one that is realistic for the patient and that will prevent diabetic complications for as long as possible.

References
1. US Department of Health and Human Services, National Diabetes Education Program. Guiding Principles for Diabetes Care for Healthcare Professionals (2009). www.ndep.nih.gov/media/guid prin_hc_eng.pdf. Accessed January 24, 2013.

2. National Diabetes Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Insulin resistance and prediabetes (2011). http://diabetes.niddk.nih.gov/dm/pubs/insulinresistance. Accessed January 25, 2013.

3. Hayes C, Kriska A. Role of physical activity in diabetes management and prevention. J Am Diet Assoc. 2008;108(4 suppl 1):S19-S23.

4. American Diabetes Association. Food and fitness: weight loss (2011). www.diabetes.org/food-and-fitness/fitness/weight-loss. Accessed January 25, 2013.

5. US Department of Health and Human Services, NIH. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 reference card, 2003). www.nhlbi.nih.gov/guidelines/hyper tension/phycard.pdf. Accessed January 24, 2013.

6. Ma Y, Olendzki BC, Merriam PA, et al. A randomized clinical trial comparing low-glycemic index versus ADA dietary education among individuals with type 2 diabetes. Nutrition. 2008;24(1):45-56.

7. American Diabetes Association. Glycemic index of foods (2013). www.diabetes.org/food-and-fit ness/food/planning-meals/the-glycemic-index-of-foods.html. Accessed January 25, 2013.

8. Pariser G, Ann Demeuro M, Gillette P, Stephen W. Outcomes of an education and exercise program for adults with type 2 diabetes, and comorbidities that limit their mobility: a preliminary project report. Cardiopulm Phys Ther J. 2010;21(2):5-12.

9. American Diabetes Association. Food and fitness: create your plate (2013). www.diabetes.org/food-and-fitness/food/planning-meals/create-your-plate. Accessed January 24, 2013.

10. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17 suppl 2:1-53.

11. CDC. 2008 Physical Activity Guidelines. www.health.gov/PAGuidelines/pdf/paguide.pdf. Accessed January 24, 2013.

12. CDC. 2011 National Diabetes Fact Sheet. www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed January 25, 2013.

13. American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35 suppl 1:S11-S63.

14. Franz MJ, Powers MA, Leontos C, et al. The evidence for medical nutrition therapy for type 1 and type 2 diabetes in adults. J Am Diet Assoc. 2010;110(12):1852-1889.

15. Solomon TP, Haus JM, Kelly KR, et al. A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans. Am J Clin Nutr. 2010;92(6):1359-1368.

16. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. Diabetes Care. 2003;26(8):2261-2267.

17. Solomon TP, Haus JM, Kelly KR, et al. Randomized trial on the effects of a 7-d low–glycemic diet and exercise intervention on insulin resistance in older obese humans. Am J Clin Nutr. 2009;90(5):1222-1229.

18. Wolever TM, Gibbs AL, Mehling C, et al. The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low–glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein. Am J Clin Nutr. 2008;87(1):114-125.

19. Metkus TS, Baughman KL, Thompson PD. Exercise prescription and primary prevention of cardiovascular disease. Circulation. 2010;121(23):2601-2604.

20. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation. 2002;106(14);1883-1892.

Nearly 26 million US adults are estimated to have type 2 diabetes, including at least eight million who are unaware they have the disease.¹ An additional 80 million adults are affected by prediabetes, with above-average glucose levels that do not yet meet American Diabetes Association (ADA) criteria for type 2 diabetes.^1,2

In this context, the primary care provider is likely to encounter patients with a diagnosis of type 2 diabetes in its early stages. Which patients can be considered candidates for conservative management—that is, lifestyle modification—before antidiabetic medications are initiated?

Case Patient
A black woman, age 44, presented for a routine physical examination. She said she had been in good health until three months earlier, when she began to experience weakness and fatigue. She complained of increased thirst and frequent urination, requiring her to get up three or four times each night. She had increased her average fluid intake to nine glasses a day from the usual four. Despite a good appetite, she had lost about 7 lb over the previous three months.

The patient’s previous medical history was significant for four cesarean deliveries, gestational diabetes during all four pregnancies, hemorrhoids, constipation, keloid formation, and hyperlipidemia. Her family history was significant for diabetes (paternal side) and hyperlipidemia.

Findings from the patient’s physical exam included weight, 217 lb; height, 5’11”; BMI, 30.3; pulse, 80 beats/min and regular; and blood pressure, 138/78 mm Hg. With the exception of obesity and elevated systolic blood pressure, her physical exam findings were within normal limits.

Laboratory testing yielded the following results: urinalysis, 3+ glucose, negative for ketones and protein; fasting blood glucose, 145 mg/dL; hemoglobin A1C, 6.9%; total cholesterol, 230 mg/dL; HDL cholesterol (HDL-C), 21 mg/dL; LDL cholesterol (LDL-C), 144 mg/dL; and triglycerides, 400 mg/dL.

The patient’s history of gestational diabetes, her acknowledged sedentary lifestyle, body weight currently exceeding her ideal weight by 50 lb, and family history positive for diabetes put her at increased risk for diabetes. Also of concern was her elevated systolic blood pressure.

The patient’s A1C of 6.9% indicated that during the previous two months, her average blood glucose had been in excess of 125 mg/dL. A diagnosis of type 2 diabetes was made, based on the patient’s elevated fasting blood glucose and A1C, and the aforementioned symptoms of weight loss, fatigue, polydypsia, and polyuria. 

Because the patient was perceived as self-reliant and responsible, it was recommended that she be treated conservatively with a broad lifestyle modification regimen. Goals were to reduce all of her diabetes indicators, including weight,^3,4 blood pressure,⁵ and A1C, with an improved lipids profile—all, if possible, without the use of medication. The regimen comprised a low–glycemic index (GI) diet^6,7 to reduce her glucose level, and aerobic exercise and strength training⁸ to improve her cardiovascular health. With resulting weight loss and reduced salt intake,^3-5 it was expected that the patient would see reductions in her total cholesterol, LDL-C, and systolic blood pressure.

The patient’s management team recommended a daily plan of four small meals and one or two small snacks. She was advised to control portions by visually dividing her plate: Non-starchy (low-GI) vegetables should fill half of the plate, with the remaining half divided into equal sections for a small serving of protein and a small serving of carbohydrates with a GI of 55 or less (see figure^7,9).

Her exercise program was based on recommendations from the American Association of Clinical Endocrinologists (AACE)¹⁰ and the US Department of Health and Human Services¹¹: cardiovascular/aerobic exercise (five 30-minute sessions per week), ranging in intensity from moderate (eg, brisk walking, bicycling, doubles tennis) to vigorous (jogging or running, swimming laps, singles tennis); and strength training (two 30-minute sessions per week), such as weight-lifting, push-ups, and sit-ups.

Discussion
Type 2 diabetes mellitus affects an estimated 25.8 million residents of the United States, including an estimated 8.3 million who have not yet been diagnosed.¹ According to the CDC,¹² prevalence of diabetes is greatest in black and Hispanic women and men.

The sixth leading cause of death in the US, diabetes is also the leading cause of blindness (ie, diabetic retinopathy), kidney disease requiring dialysis, and lower-limb amputation. Diabetes is closely associated with cardiovascular disease (CVD), the leading cause of death in the US.¹² Other diabetes-related health concerns include hypertension, peripheral diabetic neuropathy, dental disease, depression, delayed wound healing, and increased risk for infection.¹²

The standard criteria for a diagnosis of diabetes, according to the 2012 ADA Standards of Medical Care in Diabetes,¹³ are:

• A1C exceeding 6.5%, or
• A fasting blood glucose level at or exceeding 126 mg/dL, or

• A 2-hour plasma glucose at or exceeding 200 mg/dL during an oral glucose tolerance test, or

• A random blood glucose of 200 mg/dL or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis.¹³

Treatment Goals
Goals for diabetic patients advocated by the National Diabetes Education Program (NDEP)¹ include maintaining blood pressure below 130/80 mm Hg, lowering LDL-C to below 100 mg/dL (and below 70 mg/dL in patients at risk for CVD), reducing triglyceride levels to below 150 mg/dL, and raising HDL-C above 40 mg/dL in women and above 50 mg/dL in men. Achieving these levels can reduce the diabetic patient’s risk for CVD and microvascular complications by 50%.¹

Medical Nutrition Therapy
The NDEP and other entities^1,14 refer to medical nutrition therapy as an integral component of diabetic management. This individualized meal plan, developed by a registered dietitian, is based on the patient’s nutritional status and preferences. To optimize the case patient’s glycemic control,¹⁰ a low-GI diet was selected.

As the ADA⁹ and Solomon et al¹⁵ have explained, this diet is based on foods that produce a reduced glucose response during the two hours after consumption. According to one literature review,¹⁶ use of a low-GI diet led a reduction in A1C of 0.43 percentage points. When combined with appropriate exercise, the low-GI diet can alleviate hypertension and postprandial hyperinsulinemia,^15,17 as well as levels of C-reactive protein, an inflammatory marker that in high concentrations is associated with increased risk for CVD.¹⁸

The Role of Exercise
The ADA 2012 standards¹³ recommend a minimum of 150 minutes per week of moderate physical activity. The benefits of exercise in diabetic patients include improved control of blood glucose and reduction of risk for heart disease and other illnesses.^3,11 Patients should be under the care of a provider who can help develop an appropriate, individualized plan.^3,11

According to ADA recommendations,¹³ the patient’s lipid levels, blood pressure, and smoking status should be evaluated, with assessment for the presence of CVD in at-risk patients. For asymptomatic diabetic patients, the American College of Cardiology/American Heart Association recommend an ECG stress test before an exercise program is undertaken.^19,20 Exercise is contraindicated in those with decompensated congestive heart failure, complex ventricular arrhythmias, unstable angina, significant aortic stenosis, or aortic aneurysm.¹⁹

Because initiating an exercise program incurs a slight risk for injury, patients should start gradually, warming up before each session and cooling down afterward.^11,19 Diabetic patients should also wear proper shoes for maximum foot protection. They must also be instructed to watch for signs of hypoglycemia during physical activity and be prepared to treat it.^11,13

Patient Outcome
After one year on her prescribed treatment regimen, the patient’s A1C was measured at 6.3%, and her LDL-C was 124 mg/dL. Another year later, her A1C was further reduced to 5.9%, and her LDL-C to 77.2 mg/dL. By then, she had lost 15 lb (BMI, 28.2) and perceived her current maintenance plan as enjoyable and manageable, long-term: She was exercising every day possible, with seven sessions of at least 30 minutes, and maintaining a diet of low-GI foods. The patient was committed to following up with her clinician for glucose monitoring every three months.

Conclusion
As illustrated in this patient’s case, the best plan for management of diabetes in its early stages is one that is realistic for the patient and that will prevent diabetic complications for as long as possible.

References
1. US Department of Health and Human Services, National Diabetes Education Program. Guiding Principles for Diabetes Care for Healthcare Professionals (2009). www.ndep.nih.gov/media/guid prin_hc_eng.pdf. Accessed January 24, 2013.

2. National Diabetes Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Insulin resistance and prediabetes (2011). http://diabetes.niddk.nih.gov/dm/pubs/insulinresistance. Accessed January 25, 2013.

3. Hayes C, Kriska A. Role of physical activity in diabetes management and prevention. J Am Diet Assoc. 2008;108(4 suppl 1):S19-S23.

4. American Diabetes Association. Food and fitness: weight loss (2011). www.diabetes.org/food-and-fitness/fitness/weight-loss. Accessed January 25, 2013.

5. US Department of Health and Human Services, NIH. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 reference card, 2003). www.nhlbi.nih.gov/guidelines/hyper tension/phycard.pdf. Accessed January 24, 2013.

6. Ma Y, Olendzki BC, Merriam PA, et al. A randomized clinical trial comparing low-glycemic index versus ADA dietary education among individuals with type 2 diabetes. Nutrition. 2008;24(1):45-56.

7. American Diabetes Association. Glycemic index of foods (2013). www.diabetes.org/food-and-fit ness/food/planning-meals/the-glycemic-index-of-foods.html. Accessed January 25, 2013.

8. Pariser G, Ann Demeuro M, Gillette P, Stephen W. Outcomes of an education and exercise program for adults with type 2 diabetes, and comorbidities that limit their mobility: a preliminary project report. Cardiopulm Phys Ther J. 2010;21(2):5-12.

9. American Diabetes Association. Food and fitness: create your plate (2013). www.diabetes.org/food-and-fitness/food/planning-meals/create-your-plate. Accessed January 24, 2013.

10. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17 suppl 2:1-53.

11. CDC. 2008 Physical Activity Guidelines. www.health.gov/PAGuidelines/pdf/paguide.pdf. Accessed January 24, 2013.

12. CDC. 2011 National Diabetes Fact Sheet. www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed January 25, 2013.

13. American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35 suppl 1:S11-S63.

14. Franz MJ, Powers MA, Leontos C, et al. The evidence for medical nutrition therapy for type 1 and type 2 diabetes in adults. J Am Diet Assoc. 2010;110(12):1852-1889.

15. Solomon TP, Haus JM, Kelly KR, et al. A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans. Am J Clin Nutr. 2010;92(6):1359-1368.

16. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. Diabetes Care. 2003;26(8):2261-2267.

17. Solomon TP, Haus JM, Kelly KR, et al. Randomized trial on the effects of a 7-d low–glycemic diet and exercise intervention on insulin resistance in older obese humans. Am J Clin Nutr. 2009;90(5):1222-1229.

18. Wolever TM, Gibbs AL, Mehling C, et al. The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low–glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein. Am J Clin Nutr. 2008;87(1):114-125.

19. Metkus TS, Baughman KL, Thompson PD. Exercise prescription and primary prevention of cardiovascular disease. Circulation. 2010;121(23):2601-2604.

20. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation. 2002;106(14);1883-1892.

Nearly 26 million US adults are estimated to have type 2 diabetes, including at least eight million who are unaware they have the disease.¹ An additional 80 million adults are affected by prediabetes, with above-average glucose levels that do not yet meet American Diabetes Association (ADA) criteria for type 2 diabetes.^1,2

In this context, the primary care provider is likely to encounter patients with a diagnosis of type 2 diabetes in its early stages. Which patients can be considered candidates for conservative management—that is, lifestyle modification—before antidiabetic medications are initiated?

Case Patient
A black woman, age 44, presented for a routine physical examination. She said she had been in good health until three months earlier, when she began to experience weakness and fatigue. She complained of increased thirst and frequent urination, requiring her to get up three or four times each night. She had increased her average fluid intake to nine glasses a day from the usual four. Despite a good appetite, she had lost about 7 lb over the previous three months.

The patient’s previous medical history was significant for four cesarean deliveries, gestational diabetes during all four pregnancies, hemorrhoids, constipation, keloid formation, and hyperlipidemia. Her family history was significant for diabetes (paternal side) and hyperlipidemia.

Findings from the patient’s physical exam included weight, 217 lb; height, 5’11”; BMI, 30.3; pulse, 80 beats/min and regular; and blood pressure, 138/78 mm Hg. With the exception of obesity and elevated systolic blood pressure, her physical exam findings were within normal limits.

Laboratory testing yielded the following results: urinalysis, 3+ glucose, negative for ketones and protein; fasting blood glucose, 145 mg/dL; hemoglobin A1C, 6.9%; total cholesterol, 230 mg/dL; HDL cholesterol (HDL-C), 21 mg/dL; LDL cholesterol (LDL-C), 144 mg/dL; and triglycerides, 400 mg/dL.

The patient’s history of gestational diabetes, her acknowledged sedentary lifestyle, body weight currently exceeding her ideal weight by 50 lb, and family history positive for diabetes put her at increased risk for diabetes. Also of concern was her elevated systolic blood pressure.

The patient’s A1C of 6.9% indicated that during the previous two months, her average blood glucose had been in excess of 125 mg/dL. A diagnosis of type 2 diabetes was made, based on the patient’s elevated fasting blood glucose and A1C, and the aforementioned symptoms of weight loss, fatigue, polydypsia, and polyuria. 

Because the patient was perceived as self-reliant and responsible, it was recommended that she be treated conservatively with a broad lifestyle modification regimen. Goals were to reduce all of her diabetes indicators, including weight,^3,4 blood pressure,⁵ and A1C, with an improved lipids profile—all, if possible, without the use of medication. The regimen comprised a low–glycemic index (GI) diet^6,7 to reduce her glucose level, and aerobic exercise and strength training⁸ to improve her cardiovascular health. With resulting weight loss and reduced salt intake,^3-5 it was expected that the patient would see reductions in her total cholesterol, LDL-C, and systolic blood pressure.

The patient’s management team recommended a daily plan of four small meals and one or two small snacks. She was advised to control portions by visually dividing her plate: Non-starchy (low-GI) vegetables should fill half of the plate, with the remaining half divided into equal sections for a small serving of protein and a small serving of carbohydrates with a GI of 55 or less (see figure^7,9).

Her exercise program was based on recommendations from the American Association of Clinical Endocrinologists (AACE)¹⁰ and the US Department of Health and Human Services¹¹: cardiovascular/aerobic exercise (five 30-minute sessions per week), ranging in intensity from moderate (eg, brisk walking, bicycling, doubles tennis) to vigorous (jogging or running, swimming laps, singles tennis); and strength training (two 30-minute sessions per week), such as weight-lifting, push-ups, and sit-ups.

Discussion
Type 2 diabetes mellitus affects an estimated 25.8 million residents of the United States, including an estimated 8.3 million who have not yet been diagnosed.¹ According to the CDC,¹² prevalence of diabetes is greatest in black and Hispanic women and men.

The sixth leading cause of death in the US, diabetes is also the leading cause of blindness (ie, diabetic retinopathy), kidney disease requiring dialysis, and lower-limb amputation. Diabetes is closely associated with cardiovascular disease (CVD), the leading cause of death in the US.¹² Other diabetes-related health concerns include hypertension, peripheral diabetic neuropathy, dental disease, depression, delayed wound healing, and increased risk for infection.¹²

The standard criteria for a diagnosis of diabetes, according to the 2012 ADA Standards of Medical Care in Diabetes,¹³ are:

• A1C exceeding 6.5%, or
• A fasting blood glucose level at or exceeding 126 mg/dL, or

• A 2-hour plasma glucose at or exceeding 200 mg/dL during an oral glucose tolerance test, or

• A random blood glucose of 200 mg/dL or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis.¹³

Treatment Goals
Goals for diabetic patients advocated by the National Diabetes Education Program (NDEP)¹ include maintaining blood pressure below 130/80 mm Hg, lowering LDL-C to below 100 mg/dL (and below 70 mg/dL in patients at risk for CVD), reducing triglyceride levels to below 150 mg/dL, and raising HDL-C above 40 mg/dL in women and above 50 mg/dL in men. Achieving these levels can reduce the diabetic patient’s risk for CVD and microvascular complications by 50%.¹

Medical Nutrition Therapy
The NDEP and other entities^1,14 refer to medical nutrition therapy as an integral component of diabetic management. This individualized meal plan, developed by a registered dietitian, is based on the patient’s nutritional status and preferences. To optimize the case patient’s glycemic control,¹⁰ a low-GI diet was selected.

As the ADA⁹ and Solomon et al¹⁵ have explained, this diet is based on foods that produce a reduced glucose response during the two hours after consumption. According to one literature review,¹⁶ use of a low-GI diet led a reduction in A1C of 0.43 percentage points. When combined with appropriate exercise, the low-GI diet can alleviate hypertension and postprandial hyperinsulinemia,^15,17 as well as levels of C-reactive protein, an inflammatory marker that in high concentrations is associated with increased risk for CVD.¹⁸

The Role of Exercise
The ADA 2012 standards¹³ recommend a minimum of 150 minutes per week of moderate physical activity. The benefits of exercise in diabetic patients include improved control of blood glucose and reduction of risk for heart disease and other illnesses.^3,11 Patients should be under the care of a provider who can help develop an appropriate, individualized plan.^3,11

According to ADA recommendations,¹³ the patient’s lipid levels, blood pressure, and smoking status should be evaluated, with assessment for the presence of CVD in at-risk patients. For asymptomatic diabetic patients, the American College of Cardiology/American Heart Association recommend an ECG stress test before an exercise program is undertaken.^19,20 Exercise is contraindicated in those with decompensated congestive heart failure, complex ventricular arrhythmias, unstable angina, significant aortic stenosis, or aortic aneurysm.¹⁹

Because initiating an exercise program incurs a slight risk for injury, patients should start gradually, warming up before each session and cooling down afterward.^11,19 Diabetic patients should also wear proper shoes for maximum foot protection. They must also be instructed to watch for signs of hypoglycemia during physical activity and be prepared to treat it.^11,13

Patient Outcome
After one year on her prescribed treatment regimen, the patient’s A1C was measured at 6.3%, and her LDL-C was 124 mg/dL. Another year later, her A1C was further reduced to 5.9%, and her LDL-C to 77.2 mg/dL. By then, she had lost 15 lb (BMI, 28.2) and perceived her current maintenance plan as enjoyable and manageable, long-term: She was exercising every day possible, with seven sessions of at least 30 minutes, and maintaining a diet of low-GI foods. The patient was committed to following up with her clinician for glucose monitoring every three months.

Conclusion
As illustrated in this patient’s case, the best plan for management of diabetes in its early stages is one that is realistic for the patient and that will prevent diabetic complications for as long as possible.

References
1. US Department of Health and Human Services, National Diabetes Education Program. Guiding Principles for Diabetes Care for Healthcare Professionals (2009). www.ndep.nih.gov/media/guid prin_hc_eng.pdf. Accessed January 24, 2013.

2. National Diabetes Information Clearinghouse, National Institute of Diabetes and Digestive and Kidney Diseases, NIH. Insulin resistance and prediabetes (2011). http://diabetes.niddk.nih.gov/dm/pubs/insulinresistance. Accessed January 25, 2013.

3. Hayes C, Kriska A. Role of physical activity in diabetes management and prevention. J Am Diet Assoc. 2008;108(4 suppl 1):S19-S23.

4. American Diabetes Association. Food and fitness: weight loss (2011). www.diabetes.org/food-and-fitness/fitness/weight-loss. Accessed January 25, 2013.

5. US Department of Health and Human Services, NIH. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 reference card, 2003). www.nhlbi.nih.gov/guidelines/hyper tension/phycard.pdf. Accessed January 24, 2013.

6. Ma Y, Olendzki BC, Merriam PA, et al. A randomized clinical trial comparing low-glycemic index versus ADA dietary education among individuals with type 2 diabetes. Nutrition. 2008;24(1):45-56.

7. American Diabetes Association. Glycemic index of foods (2013). www.diabetes.org/food-and-fit ness/food/planning-meals/the-glycemic-index-of-foods.html. Accessed January 25, 2013.

8. Pariser G, Ann Demeuro M, Gillette P, Stephen W. Outcomes of an education and exercise program for adults with type 2 diabetes, and comorbidities that limit their mobility: a preliminary project report. Cardiopulm Phys Ther J. 2010;21(2):5-12.

9. American Diabetes Association. Food and fitness: create your plate (2013). www.diabetes.org/food-and-fitness/food/planning-meals/create-your-plate. Accessed January 24, 2013.

10. Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17 suppl 2:1-53.

11. CDC. 2008 Physical Activity Guidelines. www.health.gov/PAGuidelines/pdf/paguide.pdf. Accessed January 24, 2013.

12. CDC. 2011 National Diabetes Fact Sheet. www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed January 25, 2013.

13. American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care. 2012;35 suppl 1:S11-S63.

14. Franz MJ, Powers MA, Leontos C, et al. The evidence for medical nutrition therapy for type 1 and type 2 diabetes in adults. J Am Diet Assoc. 2010;110(12):1852-1889.

15. Solomon TP, Haus JM, Kelly KR, et al. A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans. Am J Clin Nutr. 2010;92(6):1359-1368.

16. Brand-Miller J, Hayne S, Petocz P, Colagiuri S. Low-glycemic index diets in the management of diabetes: a meta-analysis of randomized controlled trials. Diabetes Care. 2003;26(8):2261-2267.

17. Solomon TP, Haus JM, Kelly KR, et al. Randomized trial on the effects of a 7-d low–glycemic diet and exercise intervention on insulin resistance in older obese humans. Am J Clin Nutr. 2009;90(5):1222-1229.

18. Wolever TM, Gibbs AL, Mehling C, et al. The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low–glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein. Am J Clin Nutr. 2008;87(1):114-125.

19. Metkus TS, Baughman KL, Thompson PD. Exercise prescription and primary prevention of cardiovascular disease. Circulation. 2010;121(23):2601-2604.

20. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1997 Exercise Testing Guidelines). Circulation. 2002;106(14);1883-1892.