Diabetes Mellitus in HIV and Aging (Updated 3/31/17)

  • The most important prevention for adult onset diabetes mellitus is to avoid excess weight gain. Since most patients living with HIV come into care at or below normal weight, patients initiating ART should be encouraged to avoid excess weight gain.
  • Screening for diabetes should be done regularly, before and after the initiation of ART, using glycosylated hemoglobin with appropriate follow up. For patients with diabetes, hemoglobin should be checked at least twice yearly.
  • The target glycosylated hemoglobin should be 8% for frail patients, especially if their life expectancy is less than 5 years, are at high risk for hypoglycemia, polypharmacy or drug interactions.
  • Management and treatment of diabetes mellitus and its complications should be done according to established guidelines.

The incidence of type 2 diabetes mellitus is reported to be as much as four times higher in patients living with HIV compared to uninfected patients and increases with increasing age. The incidence of the metabolic syndrome is also higher. The increase in risk in ART- treated patients may be related to the use of certain antiretroviral drugs, such as thymidine analogues and protease inhibitors [1, 2], obesity, hepatitis C coinfection. It appears that newer protease inhibitors and integrase strand transfer inhibitors do not promote glucose intolerance [3]. Prevention of diabetes is similar to the approach in uninfected older patients, focusing on lifestyle changes such as weight loss, aerobic exercise and proper diet. Screening for glucose intolerance should be performed regularly, before and after initiation of ART [4]. There is some debate on whether screening should be done with fasting blood glucose levels (FBG) or using glycated hemoglobin. The American Diabetes Association has recommended that glycated hemoglobin is an acceptable screening tool, with a diagnosis of diabetes when the glycated hemoglobin is equal to or greater than 6.5% [5]. However, studies have shown that while this test is highly specific, it is insensitive and should be combined with FBG (≥ 126) for screening [6, 7]. Management of patients may include switching to less glucose intolerant antiretroviral drugs and following the American Diabetes Association guidelines [5]. For younger patients and healthy older patients, the target glycated hemoglobin should less than 7% [5]  but should be increased to 8% for frail patients, especially if their life expectancy is less than 5 years, are at high risk for hypoglycemia, polypharmacy or drug interactions [8] . Recent studies have shown no benefit and possible harm from tight glucose control in type 2 diabetes mellitus [9]. The glycated hemoglobin should be checked at least twice yearly. Care of patients living with both HIV and diabetes should focus on prevention of complications (such as foot ulcers, retinopathy, hypertension and vascular disease) as much as with HIV-uninfected patients. Renal function and presence of proteinuria should also be carefully monitored as both diabetes and HIV increase the risk of renal disease. Luckily the incidence of end stage renal disease due to diabetes in patients living with HIV has declined [10].  There is increasing prevalence of obesity in the older population and since obesity is a risk factor for development of the metabolic syndrome and hyperglycemia, clinicians should counsel their older patients living with HIV to maintain proper BMI. In one cohort study, the increase in body mass following the initiation of ART was associated with an increased risk of diabetes [11].

Morphologic changes are common in older patients living with HIV/AIDS. Increasing age is risk factor for loss of subcutaneous fat (lipoatrophy) and/or increase in central fat deposition (lipohypertrophy) but newer ART regimens are less likely to promote these changes. Older patients should be switched from thymidine analogues to INSTI’s which are less likely to cause morphologic changes.   Treatment options for patients with lipohypertrophy can include surgical removal of fat or use of growth hormone or analogues.

Treatment of Diabetes Mellitus

Lifestyle modification (diet and exercise) should be the first step in managing patients with diabetes.   Pharmacologic treatment of diabetes for patients living with HIV follows the same guidelines as for those patients without HIV.  Metformin, which will result in a 1% decline in glycosylated hemoglobin, should be the first-line medication, unless there is a contraindication such as significant renal insufficiency (eGFR<30ml/min).  Sulfonylureas, incretins or insulin can be used as second agents if necessary.  Saxagliptin, a DPP-4 inhibitor, should be used with caution with CYP3A inhibitors [12].

Assessment and Treatment of Complications of Diabetes

The approach to screening for and managing the complications of diabetes in patients living with HIV are similar to those in uninfected patients.  Screening for hypertension, renal disease, hyperlipidemia, microvascular complications (retinopathy, neuropathy and nephropathy) need to be done on a regular basis.  The JNC 8 guidelines recommend treating systolic pressures above 140 and diastolic pressures above 90 [7].  BP targets for frail elderly can be higher due to the increased risk of orthostatic hypotension.  Unless contraindicated, aspirin therapy should be initiated.  For the treatment of hyperlipidemia, pitavastatin is the only oral lipid lowering agent that does not interact with ART [12].  Lower dose atorvastatin may also be used.  Pregabalin and duloxetine are recommended as initial treatment for painful peripheral neuropathy.  Gabapentin may be considered but it does have an approved indication for this [13].

Updated by

Jonathan S. Appelbaum

March 31, 2017

References

  1. Llibre JM, Falco V, Tural C, Negredo E, Pineda JA, Munoz J, et al. The changing face of HIV/AIDS in treated patients. Curr HIV Res 2009,7:365-377.
  2. De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, et al. Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care 2008,31:1224-1229.
  3. Rasmussen LD, Mathiesen ER, Kronborg G, Pedersen C, Gerstoft J, Obel N. Risk of diabetes mellitus in persons with and without HIV: a Danish nationwide population-based cohort study. PLoS One 2012,7:e44575.
  4. Simone MJ, Appelbaum J. HIV in older adults. Geriatrics 2008,63:6-12.
  5. Chamberlain JJ, Rhinehart AS, Shaefer CF, Jr., Neuman A. Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med 2016,164:542-552.
  6. Eckhardt BJ, Holzman RS, Kwan CK, Baghdadi J, Aberg JA. Glycated Hemoglobin A(1c) as screening for diabetes mellitus in HIV-infected individuals. AIDS Patient Care STDS 2012,26:197-201.
  7. Sangarlangkarn A, Appelbaum JS. Caring for Older Adults with the Human Immunodeficiency Virus. J Am Geriatr Soc 2016,64:2322-2329.
  8. Reuben DB, Herr KA, Pacala JT, Potter JF, American Geriatrics S. Geriatrics at your fingertips. New York U6 – ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=book&rft.title=Geriatrics+at+your+fingertips&rft.au=Reuben%2C+David+B&rft.au=Herr%2C+Keela+A&rft.au=Pacala%2C+James+T&rft.au=Potter%2C+Jane+F&rft.date=2015-01-01&rft.pub=American+Geriatrics+Society&rft.externalDocID=033633299&paramdict=en-US U7 – eBook: American Geriatrics Society; 2016.
  9. Wilson C. Diabetes: ACCORD: 5-year outcomes of intensive glycemic control. Nat Rev Endocrinol 2011,7:314.
  10. Abraham AG, Althoff KN, Jing Y, Estrella MM, Kitahata MM, Wester CW, et al. End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis 2015,60:941-949.
  11. Achhra AC, Mocroft A, Reiss P, Sabin C, Ryom L, de Wit S, et al. Short-term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D:A:D study. HIV Med 2016,17:255-268.
  12. Monroe AK, Glesby MJ, Brown TT. Diagnosing and managing diabetes in HIV-infected patients: current concepts. Clin Infect Dis 2015,60:453-462.
  13. Pop-Busui R, Boulton AJ, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care 2017,40:136-154.
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