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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Insulin Resistance, Asymptomatic Hyperglycemia, Diabetes Mellitus

(Last updated:11/1/2012; last reviewed:11/1/2012)

Table 17f. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Insulin Resistance, Asymptomatic Hyperglycemia, Diabetes Mellitus
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Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Insulin resistance, asymptomatic hyperglycemia, DMa Thymidine analogue NRTIs (d4T, ddI, ZDV)
Some PIs (IDV, LPV/r; perhaps less often ATV, ATV/r, DRV/r, TPV/r)
Onset:
Weeks to months after beginning therapy; median of 60 days (adult data)

Presentation:
Most commonly:
Asymptomatic fasting hyperglycemia (possibly in the setting of lipodystrophy), metabolic syndrome, or growth delay

Also possible:
Frank DM (polyuria, polydipsia, polyphagia, fatigue, hyperglycemia)

Impaired fasting glucose:
ARV-treated adults: 3%–25%

ARV-treated children:
0%–7%

Impaired glucose tolerance:
ARV-treated adults: 16%–35%

ARV-treated children:
3%–4%

DM:
ARV-treated adults: 0.6–4.7 per 100 person-years (2- to 4-fold greater than that for HIV-uninfected adults)

ARV-treated children:
Very rare in HIV-infected children

Risk factors for Type 2 DM:
Lipodystrophy

Metabolic syndrome

Family history of DM

High BMI

Obesity

Prevention:
Lifestyle modification (see Management ).

Although uncertain, avoiding use of d4T, IDV may reduce risk.

Monitoring:
Monitor for polydipsia, polyuria, polyphagia, change in body habitus, acanthosis nigricans.

Obtain RPG levels at:
Initiation of ARV therapy;
3–6 months after therapy initiation; and once a year thereafter.


For RPG ≥140 mg/dL, obtain FPG performed after 8-hour fast and consider referral to endocrinologist.

Counsel on lifestyle modification (low-fat diet, exercise, no smoking).

Consider changing from thymidine analogue NRTI (d4T or ZDV)-containing regimen.

For either RPG ≥200 mg/dL plus symptoms of DM or FPG ≥126 mg/dL:
Patient meets diagnostic criteria for DM; consult endocrinologist.


FPG 100–125 mg/dL:
Impaired FPG is suggestive of insulin resistance; consult endocrinologist.

FPG <100 mg/dL:
Normal FPG but does not exclude insulin resistance; recheck FPG in 6–12 months.

a Insulin resistance, asymptomatic hyperglycemia, and DM form a spectrum of increasing severity. Insulin resistance is often defined as elevated insulin levels for the level of glucose observed; impaired FPG as an FPG of 100–125 mg/dL; impaired glucose tolerance as an elevated 2-hour PG of 140–199 mg/dL in a standard OGTT; and diabetes mellitus as either an FPG ≥126 mg/dL, a random PG ≥200 mg/dL in a patient with hyperglycemia symptoms, an HgbA1C of ≥6.5%, or a 2-hour PG after OGTT ≥200 mg/dL. However, the Panel does not recommend routine determinations of insulin levels, HgbA1C, or glucose tolerance without consultation with an endocrinologist; these guidelines are instead based on the readily available random and fasting plasma glucose levels.

Key to Acronyms: ARV = antiretroviral, ATV = atazanavir, ATV/r = atazanavir/ritonavir, d4T = stavudine, ddI = didanosine, DM = diabetes mellitus, DRV/r = darunavir/ritonavir, FPG = fasting plasma glucose, IDV = indinavir, LPV/r = lopinavir/ritonavir, NRTI = nucleoside reverse transcriptase inhibitor, OGTT = oral glucose tolerance test, PG = plasma glucose, PI = protease inhibitor, RPG = random plasma glucose, TPV/r = tipranavir/ritonavir, ZDV = zidovudine

References

Clinical features of hyperglycemia, insulin resistance, and diabetes mellitus

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Management of hyperglycemia, insulin resistance, and diabetes mellitus

  1. American Diabetes A. Standards of medical care in diabetes—2012. Diabetes Care. Jan 2012;35 Suppl 1:S11-63. Available at http://www.ncbi.nlm.nih.gov/pubmed/22187469.
  2. Nathan DM, Buse JB, 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 of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes care. Jan 2009;32(1):193-203. Available at http://www.ncbi.nlm.nih.gov/pubmed/18945920.
  3. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes care. Mar 2007;30(3):753-759. Available at http://www.ncbi.nlm.nih.gov/pubmed/17327355.
  4. 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. J Acquir Immune Defic Syndr. Nov 1 2002;31(3):257-275. Available at http://www.ncbi.nlm.nih.gov/pubmed/12439201.
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  6. Feeney ER, Mallon PW. Insulin resistance in treated HIV infection. Best Pract Res Cl En. Jun 2011;25(3):443-458. Available at http://www.ncbi.nlm.nih.gov/pubmed/21663838.
  7. Paik IJ, Kotler DP. The prevalence and pathogenesis of diabetes mellitus in treated HIV-infection. Best Pract Res Cl En. Jun 2011;25(3):469-478. Available at http://www.ncbi.nlm.nih.gov/pubmed/21663840