for Health Care Providers
Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.
- Diabetes is an independent risk factor for CAD and significantly increases the risk of peripheral vascular disease, neuropathy, amputation, stroke, chronic kidney disease, retinopathy, glaucoma, cataracts, and dementia.
- Preventive health care is critical for patients with diabetes to reduce the risks of CV and cerebrovascular disease, limb loss, vision loss, and renal damage.
- The risk of diabetes for HIV-infected patients consists primarily of traditional factors, with possible added risk from the use of some PIs and NRTIs, which may exacerbate underlying diabetes risk.
- Primary prevention:
- Screen for diabetes and impaired fasting glucose with a fasting glucose test before starting ARVs, and 3 months after starting or changing ARVs. If initial screening results are normal, check fasting glucose annually. If impaired fasting glucose is present, check every 3-6 months.
- Encourage weight loss for patients who are overweight, and exercise for all.
- Secondary prevention:
- For treatment of Type 2 diabetes, start with monotherapy (metformin is preferred for obese patients); sequentially add other classes of oral agents. If the HbA1c goal has not been reached with use of ≥2 oral agents, add insulin.
- Rosiglitazone is no longer recommended for use owing to its potential increased risk of cardiovascular events. If a thiazolidinedione is indicated for treatment, pioglitazone is the recommended choice.
- Reduce CV risks by controlling blood pressure and lipid levels, counseling on smoking cessation, and initiating antiplatelet therapy.
- Tertiary prevention:
- Screen annually for:
- Renal disease
- Retinopathy (dilated eye examination)
- Lower extremity complications
- Screen annually for:
- Diabetes is an independent risk factor for the development of CAD and is considered a CAD risk equivalent for the purposes of lipid management and antiplatelet therapy (see Dyslipidemia).
- Diabetes significantly increases the risk of stroke, peripheral vascular disease, retinopathy, chronic kidney disease, and HIV dementia.
- Risk of diabetes for HIV-infected patients consists primarily of traditional factors (see Evaluation, below).
- Some PIs and NRTIs confer added risk of Type 2 diabetes, and these medications may exacerbate underlying diabetes risk.
- New-onset diabetes is estimated to occur in 1-6% of HIV-infected patients on PIs. In one early study, 7% of patients on PIs were diagnosed with diabetes using the oral glucose tolerance test (OGTT).
- The same study showed that an additional 16% of patients had impaired glucose tolerance (IGT).
- The pathogenesis of insulin resistance among patients on PIs is not fully understood. It is hypothesized that inhibition of the GLUT-4 insulin-stimulated glucose-transport system by some PIs plays a role.
- When NRTIs have affected fat distribution, lipolysis increases, which can lead to a higher risk of insulin resistance.
- Increased insulin resistance is seen among patients who have developed lipohypertrophy, with a dorsocervical fat pad ("buffalo hump") or increased upper chest fat or intraabdominal fat.
- Lipoatrophy is associated with higher 2- hour glucose levels on OGTT.
- Obesity is a major risk factor for Type 2 diabetes in HIV-infected persons and in the general population.
Veterans with HIV*
- Diabetes, Type 2: 15%
- Diabetes, Type 1: 3%
- Ischemic heart disease: 11%
|Impaired fasting glucose|
|Risk factors include:||Medications that increase diabetes risk include:|
Fasting glucose or glycosylated hemoglobin (HbA1c) (and fasting lipid panel) before starting ARVs
Fasting glucose or HbA1c
- 3 months after starting or changing ARVs
- Every 3-6 months for patients with IGT, to screen for diabetes and need for treatment
- Annually, if initial glucose measures are within normal limits
Consider 2-hour OGTT for patients with impaired fasting glucose or significant risk factors (eg, family history, obesity, lipoatrophy)
Standards of treatment and management of diabetes for patients with HIV generally are the same as those for diabetic patients without HIV; see below.
Emphasize behavior modification in all patients with IGT and Type 2 diabetes; see below. This includes:
- Avoiding obesity
- Weight loss for those who are overweight
- Minimizing alcohol intake
Refer all patients for basic diabetes education.
- HbA1c <7%, while avoiding hypoglycemia.
- Less-stringent goals may be appropriate for patients with advanced microvascular disease, cardiovascular disease, other comorbidities, or short life expectancy.
- Note: Recent studies in HIV-uninfected patients with Type 2 diabetes have failed to prove that patients with tighter glucose control (HbA1c <6.5%) have better CV outcomes than patients with somewhat higher HbA1c levels, and in one study, more-intensive glycemic control was associated with more CV events.
- Reduce other CV risks by controlling blood pressure and lipid levels, counseling on smoking cessation, and initiating antiplatelet therapy.
- Glycemic control may reduce microvascular disease but may not reduce risk of macrovascular events, including MI. Controlling other CV risk factors in diabetic patients is critical.
- Reduce risks of limb loss, vision loss, and renal injury.
For Type 2 diabetes, start with monotherapy (metformin is preferred for obese patients). Sequentially add other classes of oral agents if needed. If the HbA1c goal has not been reached on ≥2 oral agents, add insulin. Oral sulfonylurea should be stopped if the patient is taking insulin more than once a day.
Insulin can be considered for first-line therapy in patients presenting with HbA1c>10%, ketonuria, fasting plasma glucose ͞250 mg/dL (13.9 mmol/L), or random glucose consistently >300 mg/dL.
Note that PI-related diabetes tends to be nonketotic and usually responds to oral agents.
Self-monitoring of blood glucose (SMBG) is helpful for maintaining glycemic control in patients on oral agents and crucial in those on insulin; glucometers and test strips can be ordered through the Prosthetics Service at the local VA Medical Center.
Switching ART Regimens
- For patients who are taking ARV agents that may be causing or exacerbating hyperglycemia, consider discontinuing the problematic ARVs if safe and effective alternatives are available.
- For example, substitute ATV, an NNRTI, or integrase inhibitor in place of a PI, or an unboosted PI (eg, ATV or FPV) for an RTV-boosted PI.
- Avoid d4T.
- Before making ARV substitutions, carefully consider the possible effect on HIV virologic control and the potential adverse effects of new ARVs.
- In some cases, antidiabetic agents may still be necessary after ARV substitution.
- Reinforce lifestyle interventions at every visit.
- Check HbA1c every 3 months until the goal is reached and then at least every 6 months. The interventions should be changed if HbA1c is above goal.
- Thiazolidinediones are nonformulary within the VHA.
Figure 1. Algorithm for the Metabolic Management of Type 2 Diabetes
Management of Diabetes Mellitus
|Abbreviations: N = NPH; NPA = neutral protamine aspart; NPH = neutral protamine Hagedorn; NPL = neutral protamine lispro; R = regular|
Note: Glargine cannot be diluted or mixed with other insulins.
|Behavior modification||Reinforce at every visit|
metformin extended release
|Sulfonylureas: glipizide, glyburide|
|DPP-IV inhibitors: sitagliptin, saxagliptin|
|Glucagon-like peptide 1 agonists: exenatide, liraglutide|
|Meglitinides: repaglinide (preferred), nateglinide|
|Alpha-glucosidase inhibitors: acarbose, miglitol|
|Insulin||See below for formulations and dosing; potential adverse effects: weight gain, hypoglycemia|
|Onset||Peak (hours)||Duration (hours)|
|Insulin lispro||10-15 min||1-2||3-5|
|Insulin aspart||10-15 min||1-2||3-5|
|Short-acting: regular||0.5-1 h||2-4||4-8|
|Insulin detemir||2-3 h||None||Up to 24|
|Insulin glargine||2-3 h||None||24+|
|70/30 (70% N + 30% R)||0.5-1 h||2-10||10-18|
|75% NPL + 25% lispro||10-15 min||1-3||10-16|
|70% NPA + 30% aspart||10-15 min||1-3||10-16|
Insulin regimen selection
- Optimal insulin dosing mimics physiologic insulin release and consists of a basal component along with a prandial component, which is used to metabolize ingested carbohydrates.
- Individualization of insulin therapy is critical for ensuring optimal glycemic control.
- SMBG is critical to successful glycemic control with insulin.
- Patients should be educated regarding symptoms of hypoglycemia (eg, sweating, anxiety, disorientation, tachycardia) and instructed to ingest hard candy, juice, or another rapidly absorbed glucose source if symptoms occur.
- Insulin dosing for Type 1 diabetes
- First choice: glargine + premeal regular insulin (rapid-acting analogues [lispro and aspart] are preferred because of improved glycemic control and decreased risk of hypoglycemia; administer 10-15 minutes before or immediately after meals)
- Second choice: NPH or detemir 2 times per day + premeal regular insulin (lispro or aspart preferred)
- Third choice: NPH 2 times per day or at night + regular insulin (lispro or aspart) TID; the patient must not miss meals
- Starting basal dosage is 0.6 units/kg per day, given as 1 dose of glargine or divided as 2 doses of NPH or detemir; adjust dosage based on SMBG
- Starting prandial dosage is 5-10 units given 10-15 minutes before or immediately after meals; adjust dosage based on SMBG
- Insulin dosing for Type 2 diabetes (see Figure 2)
Important for reduction of macrovascular disease, including CV events
|Aspirin||81 mg daily|
|ACE inhibitor or ARB||Varies by agent|
|Hydrochlorothiazide||25 mg daily|
Monitoring and Other Prevention Strategies
|Urine albumin/Cr ratio|
|Retinal eye examination|
|Counseling on diet, weight loss, and exercise|
When to Refer
- Refer all patients with diabetes for education.
- All patients with Type 1 diabetes:
- Should be referred to a diabetes clinic with multidisciplinary resources (eg, diabetologist, diabetes nurse, educator/manager, and registered dietitian) for institution and adjustment of insulin therapy.
- If expeditious referral is not possible, the primary care provider should institute "survival" insulin therapy: see Insulin dosing for Type 1 diabetes under Insulin Regimen Selection.
- Refer to Podiatry for foot lesions, ingrown toenails, foot deformities, or protective footwear.
- Refer to Vascular Surgery for evaluation of arterial insufficiency.
- Refer to Endocrinology for recurrent hypoglycemia or refractory hyperglycemia.
- Refer to an emergency department for patients suspected of diabetic ketoacidosis or nonketotic hyperglycemia based on orthostatic hypotension, tachycardia, disorientation, or ketotic breath.
- American Diabetes Association Position Paper. Standards of Medical Care in Diabetes 2007. Diabetes Care. 2007 Jan;30 Suppl 1:S4-S41.
- Boulton AJ, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care. 2008 Aug;31(8):1679-85.
- Dubé MP. Disorders of glucose metabolism in patients infected with human immunodeficiency virus. Clin Infect Dis. 2000 Dec;31(6):1467-75.
- Gerstein HC, Miller ME, Byington RP, et al; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59.
- Mooradian AD, Bernbaum M, Albert SG. Narrative review: a rational approach to starting insulin therapy. Ann Intern Med. 2006 Jul 18;145(2):125-34.
- Nathan D, Buse J, Davidson MB, et al. Medical 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. Diabetes Care. 2009 Jan;32(1):193-203.
- Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2008 Jan;31(1):173-5.
- Patel A, MacMahon S, Chalmers J, et al; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2560-72.
- Schambelan M, Benson CA, Carr A, et al. Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: Recommendations of an International AIDS Society-USA Panel. JAIDS. 2002; 31:257-275.
- VA/DoD Clinical Practice Guideline Working Group. Management of Patients with Diabetes Mellitus in the Primary Care Setting. Washington, D.C.: Department of Veterans Affairs, Office of Quality and Performance; 2003. Accessed December 15, 2008.
- Wohl DA, McComsey G, Tebas P, et al. Current concepts in the diagnosis and management of metabolic complications of HIV infection and its therapy. Clin Infect Dis. 2006 Sep 1;43(5):645-53.