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Diabetes or prediabetes develops over 12 years in almost half men with well-treated HIV.

Among 104 middle-aged men with well-treated HIV infection, diabetes * or prediabetes (high or moderately high blood sugar) developed in 46% during a 12-year study. (1) Moderate gains in abdominal (belly) fat raised the risk of diabetes or prediabetes.

Diabetes and prediabetes (Table 1) affect many men and women with HIV infection. A recent nationwide US study figured that about 1 in 10 people with HIV has diabetes, a rate higher than in the general US population. (2) A few studies have calculated how often diabetes or prediabetes develops in people taking effective antiretroviral therapy. But most of these studies tracked people for only a few years. One study determined the new-diabetes rate (incidence) through 10 years in HIV-positive people in France. (3) But that study ended almost 10 years ago.

Diabetes can lead to heart disease, kidney disease, nerve damage, and eye problems. Most of these problems are preventable by early detection and effective treatment of diabetes. Although simple blood tests can detect diabetes, about one quarter of people with diabetes in the United States don't know they have the disease. (4)

To get a better understanding of recent diabetes and prediabetes rates in people taking antiretrovirals, researchers in Australia conducted this study. They also aimed to pinpoint risk factors for new diabetes or prediabetes in people with HIV.

How the study worked. Researchers focused on HIV-positive men who entered a group in 1997 for the study of HIV complications such as diabetes. These men did not have diabetes when they entered that study, and they returned for study visits for at least 2 years and for up to 18 years (to 2015). All men were taking antiretroviral therapy when they entered the original study group, and almost all continued therapy during the study period.

All study participants had an initial fasting glucose test and an oral glucose tolerance test. Both tests measure glucose (sugar) in blood.

The men had regular fasting glucose tests over the course of the study. About 10 to 12 years after the first fasting glucose test, researchers invited participants to have another oral glucose tolerance test. Researchers can use these two tests to determine whether a person has normal blood glucose, prediabetes, or diabetes (Table 1). Researchers also collected basic health data on all participants. They used DXA scans on most men to measure total body fat and abdominal (belly) fat.

The research team used standard statistical methods to estimate (1) risk of new diabetes or prediabetes and (2) impact of abdominal fat gains on risk of diabetes or prediabetes. These analyses considered the possible impact of certain other diabetes risk factors, such as older age and length of HIV infection. In this way the researchers could be more confident that the analysis pinpointed individual risk factors for diabetes or prediabetes.

What the study found. The study involved 104 men with HIV who averaged 43 years in age when they entered this study. At that point they had HIV infection for an average 8.4 years, their group CD4 count averaged about 460, and viral loads were low. Most men, 92%, had an initially normal fasting glucose (blood sugar) test. The other 8% had prediabetes.

These men continued to have regular fasting glucose tests for an average 11.8 years. During that time, prediabetes or diabetes developed in 50 men (46%). Prediabetes developed in 37 men and diabetes in 13. The incidence (new-detection rate) of prediabetes was 24.3 per 1000 person-years, while the incidence of diabetes was 10.2 per 1000 person-years. An incidence of 10.2 per 1000 person-years means diabetes would develop in about 10 of every 1000 men every year.

Among 33 men who had an oral glucose tolerance test 10 to 12 years after entering the study, diabetes or prediabetes develop in 20 (61%): 15 had prediabetes and 5 had diabetes. Among 29 men with a normal fasting glucose result when they had the oral glucose tolerance test, 13 (45%) had prediabetes and 3 (10%) had diabetes. In other words, the oral glucose tolerance test detected abnormally high glucose levels in 55% of men who had normal glucose according to the fasting glucose test.

Fifty-eight mean had DXA scans to measure body fat over time. Twelve-month gains in abdominal fat and 2-to-4-year gains in abdominal fat were higher among men who developed abnormal glucose levels (prediabetes or diabetes) over the course of the study.

Statistical analysis identified five factors that--by themselves--led to higher risk of newly detected prediabetes or diabetes during the study: older age, higher initial fasting glucose level, higher initial glucose on the oral glucose tolerance test, 12-month abdominal fat gain, and 2-to-4-year abdominal fat gain (Figure 1). In other words, older age, starting the study with high glucose (blood sugar), or gaining belly fat during the study period raised the risk that prediabetes or diabetes would develop. Similar statistical analyses did not link any individual antiretroviral drugs to higher risk of prediabetes or diabetes.

What the findings mean for you. This study of Australian men with well-treated HIV infection appears to be the longest analysis of prediabetes and diabetes risk in people with HIV, with an average 12 years of observation. (1) The new-diabetes rate in these men was high, at 10 cases per 1000 personyears. New-diabetes rates were even higher in earlier studies of US men with HIV (47 per 1000) (5) and US women with HIV (15 to 29 per 1000). (6) In the new study, 61% of people who had an oral glucose tolerance test at the end of the study period had prediabetes or diabetes.

Everyone with HIV should realize the threat posed by diabetes. In this study older age, higher glucose (blood sugar) levels at the start of the study, and gaining belly fat predicted development of prediabetes or diabetes during the 12-year study period. And fat-gain differences between people who did or did not develop diabetes were not great-only 230 g (half a pound) after 12 months and only 320 g (three quarters of a pound) after 2 to 4 years. The researchers stress that most of these men had normal weight and none were obese. Yet gaining just a little abdominal fat boosted their risk of prediabetes or diabetes. Table 2 lists all major factors that may raise the risk of prediabetes or diabetes in people with or without HIV. The National Institute of Diabetes and Digestive and Kidney Diseases also offers a simple online diabetes risk test.

People with HIV should also know the signs and symptoms of diabetes so they can alert their HIV provider if these problems develop. The National Institute of Diabetes and Digestive and Kidney Diseases lists these diabetes symptoms:7 (1) increased thirst and urination, (2) increased hunger, (3) fatigue, (4) blurred vision, (5) numbness or tingling in feet or hands, (6) sores that do not heal, and (7) unexplained weight loss.

US HIV experts recommend testing everyone with HIV for diabetes every 6 to 12 months by measuring fasting blood glucose and/or hemoglobin A1c (HbA1c, Table 1). (8) They advise screening for diabetes before a person starts antiretroviral therapy, then 1 to 3 months after starting or changing antiretrovirals.

Know your glucose level and understand the risks. If you are carrying extra weight, losing a few pounds will help reduce the risk of diabetes and could prevent it altogether.

REFERENCES

(1.) McMahon CN, Petoumenos K, Hesse K, Carr A, Cooper D, Samaras K. High rates of incident diabetes and prediabetes are evident in men with treated HIV followed for 11 years. AIDS. 2018;32:451-459.

(2.) Hernandez-Romieu AC, Garg S, Rosenberg ES, Thompson-Paul AM, Skarbinski J. Is diabetes prevalence higher among HIV-infected individuals compared with the general population? Evidence from MMP and NHANES 2009-2010. BMJ Open Diabetes Res Care. 2017;5(1):e000304.

(3.) Capeau J, Bouteloup V, Katlama C, et al. Ten-year diabetes incidence in 1046 HIV-infected patients started on a combination antiretroviral treatment. AIDS. 2012;26:303-314.

(4.) National Institute of Diabetes and Digestive and Kidney Diseases. Diabetes. https://www.niddk.nih.gov/health- information/diabetes

(5.) Brown TT, Cole SR, Li X, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the Multicenter AIDS Cohort Study. Arch Intern Med. 2005;165:1179-1184.

(6.) Tien PC, Schneider MF, Cole SR, et al. Antiretroviral therapy exposure and incidence of diabetes mellitus in the Women's Interagency HIV Study. AIDS. 2007;21:1739-1745.

(7.) National Institute of Diabetes and Digestive and Kidney Diseases. Symptoms and causes of diabetes. https://www.niddk.nih.gov/health-information/diabetes/overview/symptoms-causes

(8.) Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58:e1-e34. https://academic.oup.com/cid/article/58/1/e1/374007
Table 1. Tests for prediabetes and diabetes

               Fasting plasma      Oral glucose       Hemoglobin A1c
                glucose            tolerance test     (HbA1c) *
                                   (OGTT) *

Normal         Below 100 mg/dL     Below 140 mg/dL     Below 5.7%
Prediabetes    100 to 125 mg/dL    140 to 199 mg/dL    5.7% to 6.4%
Diabetes       Above 125 mg/dL     Above 199 mg/dL     Above 6.4%

* The OGTT and HbA1c are both simple tests. The OGTT is the 2-hour
glucose level after a 75-g oral glucose load; the HbA1c is a
standard laboratory test that can screen for diabetes and measures
the percentage of glucose stuck to a protein in our red cells.

Source: American Diabetes Association. http://www. diabetes,
org/diabetes-basics/diagnosis/ mg/dL = milligrams per deciliter.

* Words in boldface are explained in the Technical Word List at
the end of this issue.

Table 2. Diabetes risk factors for adults

* Overweight or obesity

* Age 45 or older

* Diabetes in a parent, brother, or sister

* Black, Hispanic, Asian, Native American

* High blood pressure

* Low HDL ("good") cholesterol

* High triglycerides

* History of gestational diabetes (diabetes
developing during pregnancy)

* Not physically active

* History of heart disease or stroke

* Depression

* Polycystic ovary syndrome (a hormonal
disorder in women)

* Acanthosis nigricans (dark, thick, velvety
skin around neck or armpits)

Source: National Institute of Diabetes and Digestive and
Kidney Diseases. Risk factors for type 2 diabetes, https://
www.niddk.nih.gov/health-information/diabetes/overview/
risk-factors-tvoe-2-diabetes

Figure 1. In middle-aged men with antiretroviral-treated HIV
infection, statistical analysis linked 5 factors to higher risk of
diabetes or prediabetes. (OGTT = oral glucose tolerance test;
12-m = 12-month; 2-to-4-y = 2-to-4-year.)

Factors that raise risk of prediabetes or diabetes

Older age                        1.06
Higher initial fasting glucose   2.67
Higher initial OGTT              1.47
12-m belly fat                   2.65
2-to-4-y belly fat gain          3.16

Note: Table made from bar graph.
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Title Annotation:ARTICLE 5
Publication:HIV Treatment: ALERTS!
Date:Dec 1, 2018
Words:1780
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