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Diabetes Mellitus Screening in People with HIV


Project ECHO - UNM HIV TeleECHO Clinic Diabetes Mellitus Screening in People with HIV PGY2 Ambulatory Care Pharmacy Resident [email protected] Mark Cinquegrani, PharmD Version_12 2020 1 Conflict of Interest Disclosure Statement Speaker has no financial conflicts of interest to disclose This presentation was reviewed by UNMHSC and SCAETC faculty to ensure it meets CME guidelines. This project is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS). Under grant number U1OHA33225 (South Central AIDS Education and Training Center). It was awarded to the University of New Mexico. No percentage of this project was financed with non-governmental sources. This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government 2 Learning Objectives Recognize the different methods of diagnosing diabetes (DM). Describe how these methods may not be accurate in people with HIV (PWH). Identify other screening methods and monitoring important for patients at risk of diabetes. 3 A Review of Diabetes Mellitus In Type II Diabetes Insulin is still produced by the pancreas High levels of glucose lead to high levels of insulin Cells become resistant to circulating insulin Blood glucose in the blood is elevated 4.  Screening for DM: Blood Glucose Fasting Plasma Glucose No caloric intake for at least 8 hours Glucose 126mg/dL 2-Hour Plasma Glucose Utilizing oral glucose tolerance test (75g of glucose dissolved in water) Glucose 200mg/dL Random Plasma Glucose Any glucose reading over 200mg/dL with symptoms of hyperglycemia Screening for DM: Hemoglobin A1c Both point-of-care and laboratory blood tests are available Does not require fasting Reflects blood glucose control over three months HbA1c 6.5% Independently identifies 30% of diabetes cases HIVMA Primary Care Guidelines 2020 Random or fasting blood glucose and HbA1c should be obtained prior to starting antiretroviral therapy (ART) If random blood glucose is abnormal, obtain fasting HbA1c is no longer the recommended test for diagnosing diabetes in people with HIV on ART For measurements that do not align, repeat the tests 9 HIVMA Primary Care Guidelines 2020 National Health and Nutrition Examination Survey recommend HbA1c cutoff of 5.8% for people with HIV on ART No evidence to suggest switching antiretrovirals is beneficial Inappropriately low glycated hemoglobin values and hemolysis in PWH Non-HIV infected patients HIV-infected patients p Number of patients 1238 112 Age of patients (years) 57 15 49 10 < 0.05 Sex (M/F) (n) 736/502 88/24 < 0.0001 Sex (M/F) (%) 59.5/40.5 78.6/21.4 HbA1c (%) 6.52 1.85 5.98 1.55 < 0.005 Measured-Gly (mM) 6.95 3.23 6.62 2.42 0.28 HbA1c-Gly (mM) 7.29 3.41* 6.29 2.87 < 0.005 Characteristics of patients included in the initial retrospective study Values are expressed as mean SD. Measured-Gly was significantly different from HbA1c-Gly in the non-HIV (*, p< 0.0001) and in the HIV-infected (, p<0.0001) patients. Diop ME, et al.AIDS Res Hum Retroviruses 2006 Diop ME, et al.Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected patients.AIDS Res Hum Retroviruses 2006 The difference between HbA1c-Gly and Measured-Gly is correlated with red blood cell volume, which may be affected by antiretroviral therapy 11 Inappropriately low glycated hemoglobin values and hemolysis in PWH Associations between hemolysis and treatments in the group of 249 HIV-infected patients Hemolysis was defined by serum haptoglobin values<0.5 g/l. NRTI : Nucleoside reverse transcriptase inhibitors ; NNRTI : Non nucleoside reverse transcriptase inhibitors.. Diop ME, et al.AIDS Res Hum Retroviruses 2006 Drugs used by more than 10 patients p (2) Logistic regression analysis NRTI : any 0.006 Odds ratio Range p zidovudine (ZDV) 0.10 0.90 0.42.1 0.81 stavudine (d4T) 0.76 0.66 0.22.4 0.52 lamivudine (3TC) 0.0003 3.97 1.79.2 0.001 didanosine (ddI) 0.70 1.2 0.53.1 0.72 abacavir 0.37 1.2 0.62.3 0.64 tenofovir 0.99 1.2 0.52.6 0.73 Protease inhibitors : any 0.12 ritonavir 0.08 ritonavir/lopinavir 0.34 atazanavir 0.94 NNRTI : any 0.94 efavirenz 0.93 viramune 0.77 Trimethoprim-sulfamethoxazole 0.20 Diop ME, et al.Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected patients.AIDS Res Hum Retroviruses 2006 The difference between HbA1c-Gly and Measured-Gly is correlated with red blood cell volume, which may be affected by antiretroviral therapy 12 A1C Underestimates Glycemia in HIV Infection Increased mean corpuscular volume (MCV) as a result of NRTIs is an important factor in the relationship between A1c and glycemia Abacavir was additionally found to be associated with A1c-glucose discordance, but is not considered hemotoxic NRTI= nucleoside/nucleotide reverse transcriptase inhibitors Kim PS, Woods C, Georgoff P, et al. Diabetes Care 2009; 32:15913. Kim PS, Woods C, Georgoff P, et al. A1C underestimates glycemia in HIV infection. Diabetes Care 2009; 32:15913 13 Glycated Hemoglobin in Women with Diabetes and With and Without HIV Infection Data from the Women's Interagency HIV Study Slightly lower HbA1c values in women with HIV after adjustment for fasting glucose Difference was largely accounted for by MCV Possibly greater red blood cell turnover Higher proportion of younger cells that have not been glycated Conclusion: A1c modestly underestimated glycemic control, but was not significant after adjusting for MCV Glesby MJ, Hoover DR, Shi Q, et al. Antivir Ther 2010; 15:5717. MCV may be increased in HIV-infected women on zidovudine Glesby MJ, Hoover DR, Shi Q, et al. Glycated haemoglobin in diabetic women with and without HIV infection: data from the Women's Interagency HIV Study. Antivir Ther 2010; 15:5717 Authors commented that "non-black women had lower A1c relative to black women" but didn't explain rationale or influence of social determinants of disease so unclear the significance 14 Glycated Hemoglobin A(1c) as screening for DM in PWH Few patients were on zidovudine or stavudine Did not find that race had an effect PIs may cause HbA1c to overestimate glycemia NNRTIs may cause HbA1c to underestimate glycemia Tenofovir did not appear to have an effect Eckhardt BJ, et al. AIDS Patient Care STDS 2012; 26:197201. 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; 26:197201. Scatter plot and regression curves of fasting blood glucose and hemoglobin A1c(HbA1c) adjusted for current antiretroviral use. NRTI, nucleoside reverse transcriptase inhibitor; NNTRI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. PI=protease inhibitor 15 Inaccuracy of HbA1c among Men with HIV PI use and zidovudine use were independently associated with discordance Emtricitabine, abacavir, and lamivudine may be protective Eckhardt BJ, et al. AIDS Patient Care STDS 2012; 26:197201. Factors associated with HbA1c discordance (observedexpected HbA1c) 0.5% among HIV-infected patients in the MACS. Other factors included age, race, BMI, HCV infection, AIDS and haemoglobin. The upper 95% CI for the OR of MCV 105 fL was 25.8. Slama L, Palella FJ Jr, Abraham AG, et al. Inaccuracy of haemoglobin A1c among HIV-infected men: effects of CD4 cell count, antiretroviral therapies and haematological parameters. J Antimicrob Chemother 2014; 69:33607. 16 Summary: ART Medication Effects on HbA1c Increased MCV is associated with discordant HbA1c and fasting blood glucose, this may be a medication effect HbA1c and glycemia was discordant most often for patients on protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and zidovudine Integrase inhibitors have not been studied 17 Alternate Screening Methods Fructosamine has been indicated as a more accurate measure of glycemia levels as it was not significantly affected by antiretroviral class1 May be affected by glycated lipoproteins, bilirubin, uric acid, ascorbic acid, and vitamin E2 Measures the glycemia levels over the previous 2-3 weeks3 Diabetes cut-off at 287.5mmol/L3 Prediabetes in Patients without HIV Fasting blood glucose 100-125mg/dL 2-hour fasting glucose 140-199mg/dL HbA1c 5.8-6.4% ADA recommends at least annual monitoring Reducing Risk for Developing Diabetes Achieve and maintain 7% total weight loss Increase moderate-intensity exercise to at least 150 minutes per week Nutrition should emphasize whole grains, legumes, nuts, fruits, and vegetables with minimal refined or processed foods Smoking may increase the risk diabetes, consider cessation So what about monitoring? HbA1c is still effective for monitoring diabetes Should be monitored every 6 months Goal should be less than 7% in accordance with ADA guidelines, though can be adjusted based on patient factors Fasting blood glucose can be used in conjunction with HbA1c to confirm glycemic level References Thompson, MA, et al. Primary Care Guidance for PWH: 2020 Update by HIVMA of IDSA.CID. 2020. ADA. Standards of medical Care in Diabetes-2020 Abridged for Primary Care Providers. Clinical Diabetes. 2020;38(1):10-38. 22 Resources AETC National Clinical Consultation Center HIV Management Perinatal HIV HIV PrEP HIV PEP line HCV Management Substance Use Management Present case on ECHO [email protected] [email protected] AETC National HIV Curriculum AETC National HIV-HCV Curriculum Hepatitis C Online AETC National Coordinating Resource Center