Attention A T users. To access the menus on this page please perform the following steps. 1. Please switch auto forms mode to off. 2. Hit enter to expand a main menu option (Health, Benefits, etc). 3. To enter and activate the submenu links, hit the down arrow. You will now be able to tab or arrow up or down through the submenu options to access/activate the submenu links.

HIV/AIDS

Quick Links

Veterans Crisis Line Badge
My healthevet badge

Diabetes and HIV

for Health Care Providers

Diabetes

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Key Points

  • 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

Background

  • 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%
*Veterans in the VA HIV Clinical Case Registry in care in 2007 who had an ICD-9 code corresponding to these conditions

Definitions

StateDefinition/Diagnosis
Insulin resistance
  • Failure of target tissues to respond appropriately to insulin
  • This leads to decreased muscle uptake of glucose and sometimes to increased hepatic gluconeogenesis. Insulin production is increased to overcome the insulin resistance and maintain glucose homeostasis. Over time, even high levels of endogenous insulin may not control serum glucose levels, resulting in IGT, followed by diabetes.
Impaired fasting glucose
  • Fasting blood glucose (FBG) (>8-hour fast) = 100-125 mg/dL
IGT
  • Serum glucose 140-199 mg/dL on 2-hour OGTT (serum glucose 2 hours after intake of 75 g oral glucose)
Diabetes mellitus
  • FBG ≥126 mg/dL, or
  • Random glucose ≥200 mg/dL + symptoms, or
  • 2-hour OGTT ≥200 mg/dL
  • Results must be confirmed by retesting (any method) on a different day

Evaluation

History

Risk factors include:Medications that increase diabetes risk include:
  • Family history of diabetes
  • Increasing age
  • Obesity
  • Lipoatrophy
  • Hepatitis C
  • Medications (see list at right)
  • PIs: Most (except unboosted ATV) have been implicated, particularly:
    • IDV
    • Full-dose RTV
    • LPV/r
  • NRTIs: d4T, ddI
  • Pentamidine
  • Niacin
  • Human growth hormone
  • Corticosteroids
  • Antipsychotics: including olanzapine, quetiapine, ziprasidone

Screening

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)

Initial Evaluation of Newly Diagnosed Diabetic Patients
Physical examination
  • Blood pressure
  • Weight, height, and BMI (BMI is available through the Vitals section of the CPRS Cover Sheet; see Dyslipidemia, for BMI formula)
  • Retinal eye examination (refer to Ophthalmology for dilated examination)
  • Foot risk assessment:
    • Visual inspection of feet for breaks in skin, erythema, trauma, pallor on elevation, dependent rubor, changes in size/shape of foot, nail deformities, extensive callus, tinea pedis, edema
    • Neurologic examination:
      • Monofilament test for decreased sensation
      • Ankle reflexes
    • Peripheral pulses, presence of foot hair
    • Limb-threatening conditions: acute ischemia, foot ulceration, puncture wound, ingrown toenail, signs of systemic infection
Laboratory evaluation
  • (HbA1c): reflects glycemia over previous 3-month period
  • Fasting lipid panel
  • Electrolytes, BUN, creatinine (assess for renal function and metabolic acidosis)
  • Urine albumin/creatinine ratio (microalbuminuria: 30-299 mcg/mg; macroalbuminuria: ≥300 mcg/mg; see Renal Disease)
  • LFTs
  • TSH

Management

Basic Concepts

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
  • Diet
  • Exercise
  • Minimizing alcohol intake

Refer all patients for basic diabetes education.

Treatment goals:

  • 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

Figure 1. Algorithm for the Metabolic Management of Type 2 Diabetes

(See full figure)

Management of Diabetes Mellitus

InterventionDosageComments
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 modificationReinforce at every visit
Diet
  • 50-60% carbohydrates (preferably complex)
  • 10-20% protein
  • <30% fats (<7% saturated fats)
  • <300 mg/day of cholesterol
  • Limit trans fats
Education
  • As needed
  • Refer all patients for diabetes education
Medications
Oral agents
Biguanide: metformin



metformin extended release
  • Immediate release: start with 500 mg BID or 850 mg daily
  • Increase as needed to 850 mg TID or 1,000 mg BID (maximum of 2,550 mg/day divided into 2-3 doses)
  • Extended release: start with 500 mg daily.
  • May increase by 500 mg daily each week to (maximum 2,000 mg/day)
  • Lowers HbA1c by about 1.5%
  • Preferred first-line treatment for most patients, especially those with BMI >25
  • Insulin sensitizer
  • May promote weight loss, which is useful for overweight patients
  • Potential adverse effects: nausea, diarrhea, gas, abdominal pain (take with food to reduce GI effects), lactic acidosis
  • Contraindicated in renal insufficiency (men: Cr level >1.5 mg/dL; women: Cr level >1.4 mg/dL), CHF
  • For patients on NRTIs, especially d4T and ddI, there may be compounded risk of lactic acidosis
  • May improve lipoaccumulation (mixed results in studies) but may worsen lipoatrophy
  • Hold in patients about to receive IV iodinated contrast until 2-3 days after the contrast, and verification that serum Cr is normal (to reduce the risk of contrast nephropathy)
  • Hold after surgical procedures until Cr, and urine output are normal and fluid.
Sulfonylureas: glipizide, glyburide
  • Glipizide: start with 2.5-5 mg QAM; maximum of 40 mg/day (divided into 2 doses)

    OR

  • Glipizide XL 5-10 mg QAM
  • Glyburide: start with 1.25-2.5 mg QAM or BID (maximum of 20 mg/day, may be divided into 2 doses)
  • Take glipizide 30 minutes before a meal
  • Lowers HbA1c by about 1-2%
  • Increases insulin secretion
  • Hypoglycemia is the most common adverse effect; patients should be counseled to watch for symptoms and to take these agents with food.
  • Shorter-acting sulfonylureas such as glipizide and gliclazide are preferred, especially in older patients, to reduce the risk of prolonged hypoglycemia.
  • Dose cautiously in patients with renal insufficiency: glyburide is 50% renally cleared and has T½ of 10 hours; glipizide is 80% renally cleared and has T½ of 2-5 hours; start at low dosage, increase slowly; decrease dosage or discontinue if renal function worsens
  • Glipizide does not have an active metabolite; use preferentially in chronic renal failure
  • Potential adverse effects: hypoglycemia, weight gain (approx. 4-5 lb in the first year), rash, elevation of serum transaminase levels
Thiazolidinedione: pioglitazone
  • Start with 15 mg QD
  • Increase as needed, up to 45 mg QD
  • Lowers HbA1c AIC by about 0.5-1.4%
  • FDA is reviewing complications.
  • Currently not on VHA formulary; for combination therapy in selected patients
  • Not recommended for monotherapy unless:
    • Patient is intolerant of or has contraindications to both sulfonylureas and metformin; and
    • Target HbA1c is likely to be attained
  • Absolute contraindications:
    • Type 1 diabetes or prediabetes
    • CHF: NYHA Class III or IV
    • Active liver disease or ALT >2.5 times upper limit of normal
    • Jaundice or CHF on another thiazolidinedione
  • Pioglitazone is the preferred thiazolidinedione; rosiglitazone is no longer recommended by the ADA owing to studies showing an increased risk of MI and CV death
  • Monitor fluid/volume status
  • Potential adverse effects: weight gain (˜10 lbs in first year of treatment), edema, CHF; reduction in bone mineral density and increased risk of fractures; possible increased risk of MI; caution in patients with high risk of CV events (particularly with rosiglitazone).
  • May improve nonalcoholic hepatic steatosis
  • May improve lipoatrophy (mixed results in studies)
DPP-IV inhibitors: sitagliptin, saxagliptin
  • Sitagliptin 100 mg QD
    • Reduce to 50 mg QD for patients with CrCl 30-50 mL/min
    • Reduce to 25 mg QD for patients with CrCl <30 mL/min and ESRD
  • Saxagliptin 2.5-5 mg QD
  • Reduce to 2.5 mg for CrCl <50 mL/min; give dose after dialysis if on HD
  • Nonformulary in VHA; see PBM Criteria for Use
  • Primarily used as an add-on drug, but also may be used in patients with contraindications to metformin, sulfonylureas, or thiazolidinediones
  • Potential serious adverse effects include anaphylaxis, angioedema, and Stevens-Johnson syndrome
Glucagon-like peptide 1 agonists: exenatide, liraglutide
  • Exenatide 5 µg SQ BID
  • Liraglutide, start at 0.6 mg SQ QD forx 1 week, then 1.2 mg QD, maximum 1.8 mg QD
  • Use restricted to diabetes specialists in VHA; see PBM Criteria for Use
  • Add-on drug for patients not controlled on 1-2 other oral agents.
  • Induces weight loss.
  • Increased risk of pancreatitis.
Meglitinides: repaglinide (preferred), nateglinide
  • Repaglinide 0.5-4 mg PO before meals; start at 0.5 mg; titrate with caution in renal insufficiency
  • Nateglinide 60-120 mg PO TID 1-30 minutes before meals
  • Nonformulary in VHA; see PBM Criteria for Use
  • Short-acting agents that act similarly to sulfonylureas, but are somewhat less effective at lowering HbA1c
  • Generally added to metformin monotherapy; no added benefit if used with other insulin secretagogues such as sulfonylureas
  • Repaglinide can be considered first-line monotherapy in patients with contraindications to metformin and sulfonylureas.
  • Caution in patients with hepatic and/or renal insufficiency
  • Expensive
Alpha-glucosidase inhibitors: acarbose, miglitol
  • Acarbose or Miglitol: 25-100 mg PO TID at the start of each meal; start at 25 mg TID
  • Miglitol is nonformulary in VHA
  • Lowers HbA1c AIC by about 0.5-0.8%
  • Add-on drug for patients not controlled on 1-2 other oral agents
  • Main side effects are flatulence and diarrhea, which can significantly limit tolerance (and thus are not recommended by the ADA as second-line agents)
  • Acarbose contraindicated in patients with cirrhosis
InsulinSee below for formulations and dosing; potential adverse effects: weight gain, hypoglycemia
OnsetPeak (hours)Duration (hours)
Rapid acting
Insulin lispro10-15 min1-23-5
Insulin aspart10-15 min1-23-5
Short-acting: regular0.5-1 h2-44-8
Intermediate acting
NPH1-3 h4-1010-18
Lente2-4 h4-1212-20
Long acting
Insulin detemir2-3 hNoneUp to 24
Insulin glargine2-3 hNone24+
Premixed insulins
70/30 (70% N + 30% R)0.5-1 h2-1010-18
75% NPL + 25% lispro10-15 min1-310-16
70% NPA + 30% aspart10-15 min1-310-16

Print table

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)

Figure 2

Figure 2. Initiation and Adjustment of Insulin Regimes

(See full figure)

Other Therapies
Important for reduction of macrovascular disease, including CV events
InterventionDosageComments
Aspirin81 mg daily
  • Recommended as secondary prevention for patients with a history of CV disease
  • Consider as primary prevention for patients aged ≥40 with type 2 diabetes and ≥1 other CV risk factors
  • Consider for patients aged 30-40 with type 2 diabetes and other CV risk factors, and for those with type 1 diabetes
Smoking cessationN/A
  • Assess readiness at each visit
  • Refer to cessation programs when patient is ready
  • Offer adjuncts as needed (eg, nicotine patches, bupropion)
  • See Smoking Cessation
ACE inhibitor or ARBVaries by agent
  • For treatment of microalbuminuria and hypertension in diabetic patients
Hydrochlorothiazide25 mg daily
  • For treatment of hypertension

Print table

Monitoring and Other Prevention Strategies

MethodGoalComments
HbA1c
  • <7%; less-stringent control may be appropriate for patients with advanced microvascular disease, comorbidities, or short life expectancy
  • Every 3 months if not at goal or after change of medication or dosage
  • Every 6 months if at goal
SMBG
  • Postprandial goal: <180 mg/dL (for type 2 diabetes)
  • Fasting goal: 90-130 mg/dL
  • Patients on insulin: measure 3 times daily before meals until glucose is controlled; then measure once daily alternating prebreakfast, lunch, supper, and bedtime
  • Midnight SMBG may be helpful to detect hypoglycemia if FBG is persistently elevated (from the dawn phenomenon [Somogyi effect])
  • Patients not on insulin: if unstable or in poor glycemic control, measure fasting glucose several times per week, or on specified timeline; if controlled, measure 2 times/week
  • Patients should be educated regarding symptoms of hypoglycemia (eg, sweating, anxiety, disorientation, tachycardia) and instructed to ingest hard candy, juice, or other rapidly absorbed glucose source if symptoms occur
  • Note: SMBG has no benefit if not used to guide therapy
Blood pressure
  • SBP: <140 mmHg
  • DBP: <80 mmHg
Fasting lipids
  • LDL: <100 mg/dL (<70 mg/dL with CV disease)
  • HDL: >40 mg/dL
  • TG: <150 mg/dL
  • Every 3-6 months if adjusting medications
  • Annually if stable and at goal
  • Use statins or other lipid-lowering agents as indicated
  • Be aware of possible interactions between PIs and statins (see Dyslipidemia and Lipid-Lowering Medications)
  • With most PIs, rosuvastatin or pravastatin is preferred; alternatively, low dosage of atorvastatin
  • May need to increase dosage when using statins with NNRTIs
LFTs
  • ALT <2.5 times upper limit of normal
  • Monitor every 6 months in patients on sulfonylureas or statins
Urine albumin/Cr ratio
  • Slow progression of renal injury
  • Albumin/Cr ratio ≤30 mg/g
  • Microalbuminuria: urine albumin/Cr ratio >30 mg/g; confirmed with 2 out of 3 urine tests. Treat albuminuria with ACE inhibitor or ARB (see Renal Disease)
Foot examination
  • Prevention of ulcers, infections
  • Detection of neuropathy
  • Early intervention
  • Perform foot risk assessment annually (see Initial Evaluation, above)
  • Educate patient about preventive foot care
  • Refer to Podiatry as needed for lesions and protective footwear
  • Refer to Vascular Surgery for evaluation of arterial insufficiency
Retinal eye examination
  • Vision maintenance; early diagnosis of retinopathy
  • Annually, by an ophthalmologist
  • Laser therapy available for diabetic retinopathy
Influenza vaccine
  • Decreased risk of infection
  • Annually
Pneumococcus vaccine
  • Decreased risk of infection
  • Every 5 years
Counseling on diet, weight loss, and exercise
  • Improved glycemic control
  • On diagnosis and at every visit

Print table

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.

References