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Articles  |   May 2008
Aggressively Managing Type 2 Diabetes Mellitus, Hyperlipidemia, and Bone Loss
Author Notes
  • Address correspondence to Craig W. Spellman, DO, PhD, 701 W 5th St, Texas Tech University Health Sciences Center, Department of Internal Medicine, Odessa, TX 79763-4206.E-mail: craig.spellman@ttuhsc.edu 
Article Information
Cardiovascular Disorders / Endocrinology / Diabetes
Articles   |   May 2008
Aggressively Managing Type 2 Diabetes Mellitus, Hyperlipidemia, and Bone Loss
The Journal of the American Osteopathic Association, May 2008, Vol. 108, S20-S27. doi:
The Journal of the American Osteopathic Association, May 2008, Vol. 108, S20-S27. doi:
Abstract

Physicians have many options available for treating patients with type 2 diabetes mellitus (T2DM). Making decisions on types of pharmaceuticals to use and when to introduce them into the treatment regimen can be a complex process. In addition, nutrition and exercise must be considered in any comprehensive treatment plan. The author describes the case of an African American woman with uncontrolled T2DM, obesity, hyperlipidemia, low bone mass, menopausal symptoms, stage 3 chronic kidney disease, distal sensory neuropathy, and background retinopathy. An aggressive, comprehensive treatment plan developed for this patient included pharmaceuticals (triple oral therapy: metformin, pioglitazone hydrochloride, and sitagliptin phosphate), nutrition counseling (with a registered, licensed dietician), and exercise. Treatment led to substantial improvements in the patient's daytime glucose level, glycosylated hemoglobin level, and body weight at 3-month follow-up. Further interventions were needed to address the patient's hyperlipidemia and low bone mass. The author offers physician guidelines for making decisions on glycemic control for patients with T2DM and for managing hyperlipidemia. He also strongly recommends incorporating nutrition counseling by registered, licensed dietitians and exercise (preferably of a weight-bearing nature) into treatment plans for patients with T2DM, hyperlipidemia, and low bone mass.

Numerous pharmaceutical options are available for treating patients with type 2 diabetes mellitus (T2DM). These options include monotherapy, dual therapy, and triple therapy using such agents as α-glucosidase inhibitors (AGIs), basal insulin, dipeptidyl peptidase IV (DPP-IV) inhibitors, incretin mimetics, meglitinide, metformin, sulfonylureas, and thiazolidinediones (TZDs). Making decisions regarding the most effective medications to use and the most appropriate times to initiate treatment with these medications in any particular patient can be a complex process. 
Hyperlipidemia and bone loss present special problems for T2DM management. Furthermore, effective management of T2DM, hyperlipidemia, and bone loss requires incorporation of nutrition counseling and exercise into any comprehensive treatment strategy. 
The present article offers an illustrative case presentation describing a menopausal woman with uncontrolled T2DM, hyperlipidemia, and bone loss. It also includes guidelines regarding physician decisions on glycemic control and hyperlipidemia management and notes the benefits of nutrition counseling and exercise in the treatment of patients with T2DM, hyperlipidemia, and bone loss. 
Case Presentation
The patient in the current case, Marian (not her real name), is an African American woman, 53 years of age, who had T2DM that was diagnosed 5 years previous to her initial visit. According to medical records that were at least 6 months old at the time of her initial visit, her glycosylated hemoglobin (HbA1c) level was elevated, at 9.4%. Her previous treatment consisted of a rather aggressive combination pharmaceutical therapy: metformin (titrated up to 1000 mg twice daily) with pioglitazone hydrochloride (titrated up to 45 mg/d). With this treatment regimen, the patient's HbA1c level decreased to 7.0% at 3 years previous to her initial visit and was maintained at 7.2% at 6 months prior to her initial visit. 
Marian reported having meno pausal symptoms for approximately the previous 5 months. She also admitted to having little physical activity and noted that she had some recent weight gain. In addition, she said she was a nonsmoker with a family history of cardiovascular disease (CVD). Medical records indicated that her fasting plasma glucose (FPG) was at a reasonable level, 100 mg/dL to 120 mg/dL, though her daytime glucose levels were greatly elevated—between 180 and 210 mg/dL. 
In addition to using metformin and pioglitazone to manage her T2DM, Marian was taking the following medications: a lipid-lowering agent (atorvastatin calcium, 20 mg/d); an angiotensin-converting enzyme (ACE) inhibitor (lisinopril, 20 mg twice daily); hydrochlorothiazide (25 mg/d); and an antiplatelet agent (aspirin; 81 mg/d). 
Marian's pertinent physical examination and laboratory findings at her initial visit are reported in Table 1. Her height was 5 ft 5 in, and her weight was 193 lb, with a waist circumference of 38 in and a body mass index (BMI) of 31.2. Her blood pressure was controlled, at 128/78 mm Hg, and her heart rate was 76 beats per minute. The examination also revealed that Marian had mild background retinopathy and loss of distal vibratory perception (based on placement of a 128 Hz tuning fork on toe). 
Table 1
Examination and Laboratory Findings at Initial Visit

Component

Value
Examination Findings
□ Height, in 65
□ Weight, lb193
□ Body mass index 31.2
□ Blood pressure, mm Hg128/78
Laboratory Findings
□ Fasting plasma glucose, mg/dL130
□ Glycosylated hemoglobin, % 7.6
□ Thyroid-stimulating hormone1.2
Glomerular filtration rate, mL/min/m2 55
□ Comprehensive metabolic panel
— blood urea nitrogen, mg/dL 29
— creatinine, mg/dL1.1
— albumin, g/dL 3.9
Lipid profile, mg/dL
— total cholesterol215
— LDL-C 142
— HDL-C35
— triglycerides 190
DXA T Score -3
Abnormal Examination Findings
□ Mild background retinopathy
□ Loss of distal vibratory perception
 Abbreviations: DXA, Dual-energy x-ray absorptiometry test for bone mineral density; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
Table 1
Examination and Laboratory Findings at Initial Visit

Component

Value
Examination Findings
□ Height, in 65
□ Weight, lb193
□ Body mass index 31.2
□ Blood pressure, mm Hg128/78
Laboratory Findings
□ Fasting plasma glucose, mg/dL130
□ Glycosylated hemoglobin, % 7.6
□ Thyroid-stimulating hormone1.2
Glomerular filtration rate, mL/min/m2 55
□ Comprehensive metabolic panel
— blood urea nitrogen, mg/dL 29
— creatinine, mg/dL1.1
— albumin, g/dL 3.9
Lipid profile, mg/dL
— total cholesterol215
— LDL-C 142
— HDL-C35
— triglycerides 190
DXA T Score -3
Abnormal Examination Findings
□ Mild background retinopathy
□ Loss of distal vibratory perception
 Abbreviations: DXA, Dual-energy x-ray absorptiometry test for bone mineral density; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
×
Initial laboratory test results (Table 1) revealed that Marian's FPG level had increased to 130 mg/dL, and her HbA1c level had increased to 7.6%. Her thyroid-stimulating hormone level (1.2 mIU/L) indicated normal thyroid function. Her glomerular filtration rate (GFR) indicated abnormal renal function, at 55 mL/min/1.73 m2 (Table 1). This GFR was calculated using the abbreviated Modification of Diet in Renal Disease (abbreviated MDRD) system.1 In her comprehensive metabolic panel results, Marian's blood urea nitrogen was somewhat elevated, at 29 mg/dL, and the creatinine level was 1.1 mg/dL—suggestive of renal problems when considered with the GFR. Liver function test results and calcium and phosphorus levels were normal. Lipid test results indicated that Marian had mixed hyperlipidemia (Table 1). Dual-energy x-ray absorptiometry (DXA) results showed a bone mineral density T-score of –3.0 indicative of osteoporosis. 
Clinical Considerations
The following clinical issues were deduced from Marian's medical history, physical examination findings, and laboratory test results. She had uncontrolled T2DM and obesity with hyperlipidemia, though her blood pressure appeared to be controlled. She had distal sensory neuropathy and background retinopathy, as well as stage 3 chronic kidney disease. She was menopausal and had low bone mass. 
Marian was currently taking two oral agents, but her T2DM remained uncontrolled. How should her therapy be advanced? Many options were available, including sulfonylureas, meglitinides, AGIs, DPP-IV inhibitors, incretin mimetics, and basal insulin. The strategy for making such therapeutic decisions is based on data showing that oral agents and exenatide lower HbA1c levels by approximately 1% to 1.5%. When medications are combined, an additional 1% reduction in HbA1c levels is usually achieved for each additional agent. Insulin has an unlimited capacity to lower HbA1c levels.2,3 
In light of these considerations, how is the physician to decide when to add a new oral antidiabetes agent to a patient's treatment regimen or when to advance to insulin therapy? The basic rationale for making such a decision can be described as follows. If the addition of a given medication can be expected to reduce the patient's HbA1c level by 1%—and if this 1% reduction reaches the treatment goal for that patient—then that medication should be used. However, if the expected 1% HbA1c reduction from a given medication is not enough to reach the treatment goal for that patient, then the medication should not be used. In that case, insulin therapy should be started. 
The Texas Diabetes Council (TDC) Diabetes Tool Kit, which is posted on the Texas Department of Health Services Web site, includes an algorithm (Appendix)4(p5.1) that can be used for making decisions on glycemic control for patients with T2DM. This decision algorithm, which we use at the Texas Diabetes Council, is more aggressive than that presented by Nathan et al.5 Our goal is to achieve an HbA1c level of less than or equal to 6%—provided that this level can be achieved without hypoglycemia. We want the fasting self-monitored blood glucose level to be less than or equal to 100 mg/dL, and the 2-hour postprandial self-monitored blood glucose level to be less than or equal to 140 mg/dL. In addition, medical nutrition counseling and an exercise program may be incorporated into the patient's treatment plan as part of the initial intervention. 
Initial pharmaceutical intervention, as presented in the TDC algorithm,4(p5.1) consists of dual therapy if HbA1c levels are greater than or equal to 7.5%. (Monotherapy may be considered when a patient has an HbA1c level less than 7.5%.) Dual therapy options include various combinations of metformin, meglitinide, sulfonylureas, AGIs, DPP-IV inhibitors, TZDs, exenatide (an incretin mimetic), and insulin. If at the 3-month follow-up the patient's HbA1c level is less than 1% above goal, a third oral antidiabetes agent or exenatide is added to the treatment regimen. If at the 3-month follow-up that patient's HbA1c level is greater than 1% above goal, insulin is added as a third agent.4(p5.1) 
Development of Treatment Plan for Patient in Current Case
Marian continued taking metformin and pioglitazone. To help reduce the patient's HbA1c level of 7.6%, exenatide (5 μg twice daily) was added as a third pharmaceutical agent. Although most patients respond to exenatide with the typical 1%-to-1.5% decrease in HbA1c levels, a small subset of patients with very poor glycemic control has been shown to have HbA1c reductions as great as 3% to 5% when starting exenatide.6,7 Exenatide has additional potential benefits of weight loss and improvement in β-cell function, as well as no increased risk of hypoglycemia when used in combination with metformin or TZDs.6,7 
Unfortunately, Marian stopped using exenatide after 4 weeks because of gastrointestinal adverse effects (ie, vomiting). Although our experience has shown that such adverse effects are temporary in many patients using exenatide, Marian decided that the adverse effects of the medication were not worth the potential benefits. Thus, an alternative third medication needed to be found to achieve glycemic control. 
Marian had an HbA1c level of 7.6%. After her pharmaceutical options were explained to her, she decided to try a triple oral regimen of metformin, pioglitazone, and sitagliptin phosphate (a DPP-IV inhibitor). She declined insulin therapy and intended to augment the triple oral regimen with a dedicated diet, exercise, and weight loss program in order to reach the HbA1c goal of less than or equal to 6%. The efficacy of adding a DPP-IV inhibitor is well documented. Rosenstock et al8 reported a significant decrease of 0.7% in HbA1c levels with the use of sitagliptin phosphate (100 mg/d) and pioglitazone hydrochloride (30 mg/d to 45 mg/d), compared with placebo plus pioglitazone, in patients with T2DM. Goldstein et al9 reported a 2% reduction in HbA1c levels when sitagliptin phosphate (50 mg twice daily) plus metformin (1000 mg twice daily) were used, versus placebo. 
Note that these effects of adding an agent or starting dual therapy are consistent with previously discussed rules regarding the effects of combining antidiabetic agents.2,3 We do not have data on triple oral therapy with sitagliptin plus metformin plus a TZD. However, experience in our clinics supports an additional reduction in HbA1c levels of 0.5% to 1% with a third agent. 
Although sitagliptin was used as the third medication in Marian's treatment to achieve glycemic control, other medication options would have also been potentially useful. Garber et al10 found that vildagliptin (another DPP-IV inhibitor) produced an additive effect on HbA1c levels in patients with T2DM when used at a dosage of 100 mg daily and when administered with pioglitazone (45 mg/d). Thus, the additive benefits of using a DPP-IV inhibitor with a TZD agent are not unique to only one of the DPP-IV inhibitors. 
Still other medication combinations might have been effective in reaching our goal. Ahren et al11 reported that the use of vildagliptin (50 mg/d) with metformin (1500 mg/d to 3000 mg/d) had an additive effect in decreasing HbA1c levels by 1.1% (±0.2%) in patients with T2DM, compared with placebo and metformin (P<.001). Nauck et al12 reported that the use of either sitagliptin plus metformin or glipizide plus metformin resulted in reductions in HbA1c levels, but sitagliptin plus metformin had the added benefit of weight loss of approximately 5 lb. 
Diet and Exercise
To manage her T2DM effectively, Marian required comprehensive diet and exercise plans in addition to aggressive pharmaceutical treatment. Thus, she was referred to a registered, licensed dietitian for assessment, goal-setting, and meal planning, and she began regular low-intensity exercise. 
Proper medical nutrition therapy entails referral to a registered, licensed dietitian, who will initiate a program for the patient addressing a number of vital areas (Figure). The nutrition program created by a registered, licensed dietitian typically includes assessment of the patient's anthropometrics (ie, measurements of size, weight, and proportions of the body), lifestyle, and medical records (including glucose history). In addition, a psychological evaluation may be used by the dietitian to assess the patient's readiness and ability to change personal behaviors that may be contributing factors to T2DM. 
After assessment of the patient, the dietitian establishes goals and timetables for reductions in the patient's weight (of at least 5%), glucose level, lipid level, and blood pressure. Finally, the dietitian assists the patient in meal planning. A dietitian is an invaluable part of optimizing therapy for a patient with T2DM. 
A patient's nutrition program should be augmented with an exercise program. However, how is a physician to determine the level of activity most suitable for a particular patient—and if a cardiac exercise stress test needs to be performed? The algorithm used at the Texas Diabetes Council, provides a pathway for making decisions regarding this matter.4(p3.1) 
If the patient has T2DM or impaired fasting glucose levels or both—and there is evidence of CVD—a stress test should be done. If the patient has T2DM and proliferative retinopathy or peripheral neuropathy, low-intensity exercise should be prescribed. Low-intensity exercise should also be prescribed if the patient has T2DM and at least one of the following risk factors: hypertension, hyperlipidemia, smoking, family history of CVD. Marian was started on a therapy program of low-intensity exercise because she had distal sensory neuropathy. 
Figure.
Medical nutrition therapy provided by registered, licensed dietitians for patients with type 2 diabetes mellitus.
Figure.
Medical nutrition therapy provided by registered, licensed dietitians for patients with type 2 diabetes mellitus.
Patients who have T2DM but no additional risk factors or symptoms may begin a program of vigorous exercise if they are younger than 35 years. If they are 35 years of age or older, they may begin a program of moderate exercise.4(p3.1) For any patient with T2DM, a stress test should be done before advancing the patient to a higher level of activity.4(p3.1) 
Current Case Follow-Up
After 1 month of triple oral therapy, nutrition counseling, and low-intensity exercise, Marian had results as reported in Table 2. Although her FPG level was virtually unchanged (125 mg/dL), her daytime glucose level dropped substantially, from 180-210 mg/dL to an average of 155 mg/dL. Her HbA1c level showed a mild reduction, from 7.6% to 7.2%. Marian's weight also showed a mild improvement—from 193 lb to 188 lb. Her blood pressure, at 130/76 mm Hg, was in an acceptable range. Her lipid profile was essentially unchanged from baseline. The patient reported no adverse effects after 1 month. 
Table 2
Follow-up Findings

Component

Value
1 Month
□ Weight, lb 188
□ Blood pressure, mm Hg130/76
□ Fasting plasma glucose, mg/dL 125
□ Daytime plasma glucose, mg/dL155
□ Glycosylated hemoglobin, % 7.2
□ Other
— lipid profile unchanged from presentation
— no reported abnormal examination findings
3 Months
□ Weight, lb179
□ Body mass index 29.8
□ Fasting plasma glucose, mg/dL120
□ Daytime plasma glucose, mg/dL 145
□ Glycosylated hemoglobin, %6.7
□ Lipid profile, mg/dL
— total cholesterol198
— LDL-C 130
— HDL-C38
— triglycerides 148
□ Other
— no reported abnormal examination findings
 Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
Table 2
Follow-up Findings

Component

Value
1 Month
□ Weight, lb 188
□ Blood pressure, mm Hg130/76
□ Fasting plasma glucose, mg/dL 125
□ Daytime plasma glucose, mg/dL155
□ Glycosylated hemoglobin, % 7.2
□ Other
— lipid profile unchanged from presentation
— no reported abnormal examination findings
3 Months
□ Weight, lb179
□ Body mass index 29.8
□ Fasting plasma glucose, mg/dL120
□ Daytime plasma glucose, mg/dL 145
□ Glycosylated hemoglobin, %6.7
□ Lipid profile, mg/dL
— total cholesterol198
— LDL-C 130
— HDL-C38
— triglycerides 148
□ Other
— no reported abnormal examination findings
 Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
×
After 3 months of treatment (Table 2), Marian's FPG level (120 mg/dL) was still not at goal, but it was slightly reduced from the 1-month level. Her daytime glucose level continued to show improvement, reduced to an average of 145 mg/dL. This level falls within the recommended guidelines of the American Diabetes Association (<140-180 mg/dL),13 though not quite within the guidelines of the American Association of Clinical Endocrinologists (<140 mg/dL).14 Marian's HbA1c level also continued its decrease, to 6.7%, as did her weight, to 179 lb. 
Marian's 3-month lipid profile showed little sign of improvement (Table 1). However, in the setting of diabetes mellitus, it should be noted that it is important to achieve glucose goals first—before trying to manage lipid abnormalities with pharmaceuticals. Correcting secondary causes of hyperlipidemia—such as hyperglycemia, alcohol use, or hypothyroidism—is absolutely necessary before starting additional drug therapy. 
Marian's glucose, HbA1c, and weight were all at encouraging levels at 3-month follow-up (Table 1), with no adverse effects. Thus, it was deemed desirable to begin intervention for hyperlipidemia. 
Hyperlipidemia
Various medications are available for managing hyperlipidemia, including atorvastatin, fluvastatin sodium, lovastatin, pravastatin sodium, rosuvastatin calcium, simvastatin, ezetimibe, fibrate, and niacin.15-24 Any of these medications may be effective in treatment, but how is a physician to choose the most effective medication for any particular patient? 
As first described by Jones et al,15 a lipid-lowering hydroxymethylglutaryl-coenzyme A reductase inhibitor (statin) can be selected based on the desired percent reduction in low-density lipoprotein cholesterol (LDL-C). Reference to the TDC table4(p6.4) can help a physician narrow the available choices for selecting a lipid-lowering agent. For example, if a 25% reduction in LDL-C is desired, either fluvastatin, lovastatin, or pravastatin would be a wise choice. However, if a 50% reduction in LDL-C is needed, atorvastatin, rosuvastatin, or simvastatin would be a better choice.4(p6.4) 
The addition of ezetimibe to the use of a statin has been shown to reduce LDL-C levels an additional 12% to 18%.25-27 This finding is clinically important, because adverse effects from the use of statins are dose dependent. Thus, the use of ezetimibe can result in several effective doublings of a statin dose—without causing the adverse effects associated with statins.25-27 
Basic guidelines in hyperlipidemia management for patients with T2DM, as followed by the Texas Diabetes Council, can be summarized as follows: 
  • When a patient has a lipid abnormality, the secondary causes of hyperlipidemia should be addressed before initiating lipid-lowering pharmacotherapy.
  • When a patient has elevated LDL-C levels (≥100 mg/dL), a statin should be used in treatment, with the addition of ezetimibe if lipid goals are not reached.
  • When a patient has isolated low levels of high-density lipoprotein cholesterol (HDL-C<40 mg/dL), optimize lifestyle changes (ie, diet, exercise, smoking cessation) and start fibrate, niacin, fish oil, or a statin.
  • When a patient has triglyceride concentrations in the range between 150 and 199 mg/dL, optimize lifestyle changes. When triglyceride concentrations are in the range between 200 and 399 mg/dL, optimize lifestyle changes and start fibrate, niacin, and/or fish oil. When triglyceride concentrations are 400 mg/dL or greater, optimize lifestyle changes and start fibrate, niacin, and/or fish oil and (if LDL-C not at goal) a statin.
Other Considerations Requiring Referral
For some patients with T2DM, other clinical considerations may arise during treatment. Such considerations may include the need for referral to an ophthalmologist or a nephrologist for additional management of microvascular disease or the need for further management of bone loss. 
Any patient with T2DM in which the creatinine level reaches 2 to 2.5 mg/dL would be a good candidate for referral to a nephrologist.13 Referral should be made before creatinine reaches higher levels than these—that is, before kidney dialysis may become necessary. In the current case, the patient's creatinine level was only 1.1 mg/dL. Thus, intervention by a nephrologist was not necessary. 
Patients with T2DM should be referred to an ophthalmologist when ocular regions are found to be affected by microvascular disease. In the current case, the patient was known to have retinopathy. Thus, she needed to see an ophthalmologist. 
Marian received tight, aggressive treatment for T2DM, with lipid-lowering medications, blood pressure medications, and triple oral therapy for hyperglycemia, as well as nutrition counseling and an exercise plan. This type of treatment can help prevent macrovascular events and stabilize or reverse microvascular events. As Jeffrey S. Freeman, DO, reports beginning on page S5 in this supplement issue of JAOA—The Journal of the American Osteopathic Association, tight control of glucose and blood pressure in patients with T2DM can result in substantial improvements in such parameters as 24-hour urine GFR and macroalbuminuria levels. 
Bone Disease—Medications Versus Weight-Bearing Exercise
The DXA results for Marian revealed a pathologic bone mineral density T-score of –3.0. There were a number of options to consider regarding management of her low bone mass. Two options were to measure her levels of intact parathyroid hormone (PTH) and 25-hydroxy (25-OH) vitamin D. This patient had stage 3 chronic kidney disease, with a GFR of 55 mL/min/1.73 m2. Because this is early stage 3 chronic kidney disease, one might decide against PTH testing. Calcium and phosphate levels are usually normal in patients with stages 1 to 3 chronic kidney disease.28 However, some physicians recommend measuring PTH, calcium, and phosphorus levels every 12 months in patients with stage 3 chronic kidney disease.29 
In this particular case, we decided not to evaluate the patient for secondary hyperparathyroidism at this time. Rather, we decided to reevaluate her renal function after optimizing her diabetes management. If there was improvement in 3 months, testing might not be needed. If Marian's renal status did not improve, then levels of PTH and 25-OH vitamin D would be measured. 
Many physicians would likely opt for beginning treatment with a bisphosphonate to manage this patient's bone loss. Other physicians would probably begin estrogen (hormone-replacement) therapy with this patient. However, there is another option for increasing bone density—weight-bearing exercise. 
Weight-bearing exercise yields increases in bone density comparable to increases that can be achieved with medications. A meta-analysis of resistance training in premenopausal women showed variable results of 1% to 3.9% increases in the women's bone density.30,31 These results are similar to results achieved with the use of estrogen, bisphosphonates, or teraparitide. Thus, weight-bearing exercise should be considered as part of an aggressive, comprehensive treatment plan for patients with diabetes mellitus and bone loss. 
Comment
The current case involved a menopausal women with uncontrolled T2DM, hyperlipidemia, and low bone mass. Aggressive treatment with triple oral therapy (metformin, pioglitazone, and sitagliptin), as well as nutrition counseling and exercise, led to substantial improvement in her daytime glucose, HbA1c levels, and body weight at the 3-month follow-up. 
The effects of each oral antidiabetes agent are additive. To help reduce a patient's HbA1c level, exenatide can be added as a third pharmaceutical agent, though it may result in gastrointestinal adverse effects. If a patient's HbA1c level is less than 8%, a DPP-IV inhibitor may be a preferable third option for achieving glycemic control. 
Further interventions were necessary to address Marian's hyperlipidemia and low bone mass. For hyperlipidemia, a statin can be selected based on the desired percent reduction in LDL-C. The addition of ezetimibe to the use of a statin can result in several effective doublings of a statin dose—without causing the adverse effects associated with statins. 
Medical nutrition counseling by a licensed, registered dietitian and an exercise program are crucial in a comprehensive treatment plan for a patient with T2DM, hyperlipidemia, and low bone mass. Weight-bearing exercises, in particular, can achieve substantial improvements in bone mineral density. 
Aggressive, comprehensive treatment for patients with T2DM, hyperlipidemia, and low bone mass can help prevent macrovascular events and stabilize or reverse microvascular events. 
3  
Appendix
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Appendix
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GLYCEMIC CONTROL BIBLIOGRAPHY
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GLYCEMIC CONTROL BIBLIOGRAPHY
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 This article was developed in part from a lecture presented at a symposium held September 30, 2007, at a joint American College of Osteopathic Family Physicians/American Osteopathic Association program during the AOA's 112th Annual Convention and Scientific Seminar in San Diego, Calif. Titled “Achieving Glycemic Control in Type 2 Diabetes: The Role of Incretins in Meeting Old Challenges With New Strategies: An Interactive Case-Based Discussion,” this program was supported by an educational grant from Merck & Co, Inc.
 
 Dr Spellman is associate dean for research and professor of medicine in the Department of Internal Medicine at Texas Tech University Health Sciences Center at Odessa, Tex. He is also chairman of the Health Professionals Committee of the Texas Diabetes Council.
 
 Dr Spellman discloses that he serves on the speakers bureaus of Amylin Pharmaceuticals, Inc; AstraZeneca US; Novartis Pharmaceuticals Corporation; Novo Nordisk US; and sanofi-aventis US; he has participated in clinical trials with AstraZeneca US; Bristol-Myers Squibb Company; Genentech, Inc; GlaxoSmithKlein; Novartis Pharmaceutical Corporation; Pfizer Inc; and sanofiaventis US; and he has been a consultant to Amylin Pharmaceuticals, Inc; and sanofi-aventis US.
 
Health professionals—GFR calculators. National Kidney Disease Education Program Web site. Available at: http://www.nkdep.nih.gov/professionals/gfr_calculators/index.htm. Accessed March 21, 2008.
Lebovitz HE. Oral therapies for diabetic hyperglycemia [review]. Endocrinol Metab Clin North Am. 2001;30:909-933.
Riddle MC. Oral pharmacologic management of type 2 diabetes [review]. Am Fam Physician. 1999;60:2613-2620.
Texas Diabetes Council, Texas Department of State Health Services. Diabetes Tool Kit. 4th ed. Austin, TX: Texas Department of State Health Services; August 2007: 3.1, 5.1, 6.4. Publication No. E10-114. Available at: http://www.dshs.state.tx.us/diabetes/hctoolkt.shtm. Accessed March 21, 2008.
Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes [published correction appears in Diabetes Care. 2006;49:2816-2818] Diabetes Care. 2006;29:1963-1972. Available at: http://care.diabetesjournals.org/cgi/content/full/29/8/1963. Accessed March 21, 2008.
Zinman B, Hoogwerf BJ, Duran Garcia S, Milton DR, Gianconia JM, Kim DD, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial [published correction appears in Ann Intern Med. 2007;146:896] Ann Intern Med. 2007;146:477-485. Available at: http://www.annals.org/cgi/reprint/146/7/477.pdf. Accessed March 21, 2008.
Ratner RE, Maggs D, Nielsen LL, Stonehouse AH, Poon T, Zhang B, et al. Long-term effects of exenatide therapy over 82 weeks on glycaemic control and weight in over-weight metformin-treated patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2006;8:419-428.
Rosenstock J, Brazg R, Andryuk PJ, Lu K, Stein P; for the Sitagliptin Study 019 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2006;28:1556-1568.
Goldstein BJ, Feinglos MN, Lunceford JK, Johnson J, Williams-Herman DE; for the Sitagliptin 036 Study Group. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care. 2007;30:1979-1987. Epub 2007 May 7. Available at: http://care.diabetesjournals.org/cgi/content/full/30/8/1979. Accessed March 21, 2008.
Garber AJ, Schweizer A, Baron MA, Rochotte E, Dejager S. Vildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: a randomized, placebo-controlled study. Diabetes Obes Metab. 2007;9:166-174.
Ahren B, Pacini G, Foley JE, Schweizer A. Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care. 2005;28:1936-1940. Available at: http://care.diabetesjournals.org/cgi/content/full/28/8/1936. Accessed March 21, 2008.
Nauck MA, Meininger G, Sheng D, Terranella L, Stein PP; for the Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: a randomized, double-blind, non-inferiority trial. Diabetes Obes Metab. 2007;9:194-205.
American Diabetes Association. Standards of medical care in diabetes—2008. Diabetes Care. 2008;31(suppl 1):S12-S54.
American Association of Clinical Endocrinologists Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007;13(suppl 1):1-68.
Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study) [published correction appears in Am J Cardiol. 1998;82:128] Am J Cardiol. 1998;81:582-587.
Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005-2016.
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.
Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al; CARDS investigators. Primary prevention of CVD with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685-696.
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines [published correction appears in Circulation. 2004;110:763] Circulation. 2004;110:227-239. Available at: http://circ.ahajournals.org/cgi/content/full/110/2/227. Accessed May 7, 2008.
Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol. 2005;95:120-122.
Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med. 2003;37:283-290.
Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al; FIELD study investigators. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomized controlled trial [published correction appears in Lancet. 2006;368:1415] Lancet. 2005;366:1849-1861.
Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341:410-418.
Cholesterol Treatment Trialists' (CTT) Collaborators, Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Peto R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371:117-125.
Gotto AM Jr, Farmer JA. Drug insight: the role of statins in combination with ezetimibe to lower LDL cholesterol. Nat Clin Pract Cardiovasc Med. 2006;3:664-672.
Kosoglou T, Seiberling M, Statkevich P, Cutler DL, Yang B, Anderson L, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and atorvastatin. J Am Coll Cardiol. 2001;37(2 suppl A): 229A. Abstract.
Kosoglou T, Meyer I, Musiol B, Mellars L, Statkevich P, Miller MF, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Atherosclerosis. 2000;151: 135. Abstract.
Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol. 2005;16:2205-2215. Epub May 25, 2005. Available at: http://jasn.asnjournals.org/cgi/content/full/16/7/2205. Accessed May 7, 2008.
Wolf M. Improving survival for patients with chronic kidney disease. Paper presented at: 88th Annual Meeting of the Endocrine Society; June 25 , 2006; Boston, Mass.
Martyn-St James M, Carroll S. Progressive high-intensity resistance training and bone mineral density changes among premenopausal women: evidence of discordant site-specific skeletal effects [review]. Sports Med. 2006;36:683-704.
Suominen H. Muscle training for bone strength [review]. Aging Clin Exp Res. 2006;18:85-93.
Figure.
Medical nutrition therapy provided by registered, licensed dietitians for patients with type 2 diabetes mellitus.
Figure.
Medical nutrition therapy provided by registered, licensed dietitians for patients with type 2 diabetes mellitus.
Table 1
Examination and Laboratory Findings at Initial Visit

Component

Value
Examination Findings
□ Height, in 65
□ Weight, lb193
□ Body mass index 31.2
□ Blood pressure, mm Hg128/78
Laboratory Findings
□ Fasting plasma glucose, mg/dL130
□ Glycosylated hemoglobin, % 7.6
□ Thyroid-stimulating hormone1.2
Glomerular filtration rate, mL/min/m2 55
□ Comprehensive metabolic panel
— blood urea nitrogen, mg/dL 29
— creatinine, mg/dL1.1
— albumin, g/dL 3.9
Lipid profile, mg/dL
— total cholesterol215
— LDL-C 142
— HDL-C35
— triglycerides 190
DXA T Score -3
Abnormal Examination Findings
□ Mild background retinopathy
□ Loss of distal vibratory perception
 Abbreviations: DXA, Dual-energy x-ray absorptiometry test for bone mineral density; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
Table 1
Examination and Laboratory Findings at Initial Visit

Component

Value
Examination Findings
□ Height, in 65
□ Weight, lb193
□ Body mass index 31.2
□ Blood pressure, mm Hg128/78
Laboratory Findings
□ Fasting plasma glucose, mg/dL130
□ Glycosylated hemoglobin, % 7.6
□ Thyroid-stimulating hormone1.2
Glomerular filtration rate, mL/min/m2 55
□ Comprehensive metabolic panel
— blood urea nitrogen, mg/dL 29
— creatinine, mg/dL1.1
— albumin, g/dL 3.9
Lipid profile, mg/dL
— total cholesterol215
— LDL-C 142
— HDL-C35
— triglycerides 190
DXA T Score -3
Abnormal Examination Findings
□ Mild background retinopathy
□ Loss of distal vibratory perception
 Abbreviations: DXA, Dual-energy x-ray absorptiometry test for bone mineral density; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
×
Table 2
Follow-up Findings

Component

Value
1 Month
□ Weight, lb 188
□ Blood pressure, mm Hg130/76
□ Fasting plasma glucose, mg/dL 125
□ Daytime plasma glucose, mg/dL155
□ Glycosylated hemoglobin, % 7.2
□ Other
— lipid profile unchanged from presentation
— no reported abnormal examination findings
3 Months
□ Weight, lb179
□ Body mass index 29.8
□ Fasting plasma glucose, mg/dL120
□ Daytime plasma glucose, mg/dL 145
□ Glycosylated hemoglobin, %6.7
□ Lipid profile, mg/dL
— total cholesterol198
— LDL-C 130
— HDL-C38
— triglycerides 148
□ Other
— no reported abnormal examination findings
 Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
Table 2
Follow-up Findings

Component

Value
1 Month
□ Weight, lb 188
□ Blood pressure, mm Hg130/76
□ Fasting plasma glucose, mg/dL 125
□ Daytime plasma glucose, mg/dL155
□ Glycosylated hemoglobin, % 7.2
□ Other
— lipid profile unchanged from presentation
— no reported abnormal examination findings
3 Months
□ Weight, lb179
□ Body mass index 29.8
□ Fasting plasma glucose, mg/dL120
□ Daytime plasma glucose, mg/dL 145
□ Glycosylated hemoglobin, %6.7
□ Lipid profile, mg/dL
— total cholesterol198
— LDL-C 130
— HDL-C38
— triglycerides 148
□ Other
— no reported abnormal examination findings
 Abbreviations: HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol.
×
Appendix
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Appendix
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GLYCEMIC CONTROL BIBLIOGRAPHY
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GLYCEMIC CONTROL BIBLIOGRAPHY
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