68 Journal of The Association of Physicians of India ■ Vol.

68 ■ August 2020

original article

Assessment of Glycemic status, Insulin Resistance and

Hypogonadism in HIV Infected Male Patients
Sarita Bajaj1, Kamlesh Kumar Sonkar2*, Sujit Verma3, Sharad Varma4, Alok Kumar Singh5

peripheral subcutaneous fat is usually

Abstract lost. Loss of subcutaneous fat in the
face is also commonly seen. 5 Central fat
Objectives: The aim of the present study was to assess the glycemic status
is relatively preserved and also there
measured as Fasting Plasma Glucose (FPG) and glycosylated haemoglobin
is relative and absolute accumulation
(A1C); prevalence of Insulin Resistance (IR), hypogonadism and to study their
of excess visceral fat and excess
correlation with CD4 (CD4 lymphocyte) counts in HIV infected patients receiving
upper trunk fat. 5 Lipodystrophy is
ART. Correlation between percentage android fat and IR was also studied. not only a pathogenic mechanism for
Methods and materials: 84 HIV male patients as diagnosed by ELISA test aged development of IR but increases in
18 to 70 years are included in this case control study. Software IBM SPSS 20.1 visceral fat and reductions in limb fat
and Microsoft Excel 2013 was used for analysis of data. The numerical data was are independently associated with
compared using two tailed student t-test. Log transformation was used for the increased mortality in HIV infected
conversion of qualitative data (% android fat) to quantitative data so that it can patients. 6
be correlated to HOMA-IR. The level of significance was considered 0.05.
Aims and Objectives
Results: Out of total 84 patients, 19 had FPG ≥ 100. 11(13%) had Impaired
Fasting Glucose (IFG) & 8 (9.5%) had Diabetes Mellitus (DM). 20 patients had To assess the glycemic status (FPG
A1C > 5.6. Nine (10.7%) patients had Impaired Glucose Tolerance (IGT) & 11 and A1C),to study the prevalence
(13.1%) patients had DM on the basis of A1C. 11 (13.1%) patients had DM based o f I R , t o s t u d y t h e p r e va l e n c e o f
on either FPG or A1C criteria. Patients with higher percentage android fat had hypogonadism, to study the
significantly higher IR. 33 (39%) patients had hypogonadism, six patients (7.1%) a s s oc i a t i on of g l y c em i c st a t u s, I R
had primary hypogonadism; 24 (28.6%) had secondary hypogonadism & 3 (3.6 and hypogonadism with CD4 counts
%) had compensatory hypogonadism. and to study the correlation between
percentage android fat (as marker of
Conclusion: Patients with lower CD4 counts had significantly higher dysglycemia
central obesity) and IR.
and IR. Serum testosterone levels were progressively lower (insignificant) with
decreasing CD4 counts. Materials and Methods
The case control study was
conducted in Swaroop Rani Nehru
Introduction an early diagnosis of IR could allow for h os p i ta l , M oti L a l N eh ru Me d i c a l
appropriate intervention that would College, Allahabad from May 2016 to

H IV infection causes abnormalities

in the function of almost all
endocrine organ systems of human
body. Incidence of HIV related
endocrinopathies is on the rise. This
is mainly because of HIV infection
pandemic as well as survival benefit
provided by widespread Anti-Retroviral
Therapy (ART) coverage throughout the
world. 1Various mechanisms contribute
to the development of IR, IGT, IFG and
DM, most notably the underlying HIV
infection, the contribution of different
ART drugs, weight gain associated
with the treatment, restoration of
immune system, as well as non-HIV
related factors. 2 IR is the primary
mechanism which contributes to the
development of DM in HIV infected
patients. Detection of IR, IGT and Type
2 DM (T2DM) should be systematic as
prevent progression to T2DM. 3
Hypogonadism in HIV infected
August 2017. All diagnosed HIV male
patients on ART aged 18 to 70 years
males may be attributed to both attending the Medicine Department
primary (testicular failure) and (inpatient and outpatient) and ART
secondary (hypothalamic and pituitary centre were included in the study.
failure) mechanisms. However, Patients with prior treatment (referred
secondary hypogonadism (decreased or documented) with androgens, sex
or inappropriately normal level steroids, dehydroepiandrosterone,
of gonadotropins in the setting of antiandrogens, anabolic agents,
decreased testosterone TT) 4 is more gonadotropin agonists and psycholeptic
common mechanism. Patients with agents, known cases of DM, patients with
advanced HIV disease complain of loss hyperprolactinemia, hypothyroidism,
of libido and impotence. liver insufficiency, chronic renal failure,
HIV infection is associated with and tuberculosis were excluded from
lipodystrophy. Abdominal and the study. Venous blood was collected
1
Professor, 2Associate Professor, 3Associate Professor, PG Department of Medicine, 4Senior Medical Officer, ART Centre, 5Junior
Resident, PG Department of Medicine, MLN Medical College, Prayagaraj, Uttar Pradesh; *Corresponding Author
Received: 12.09.2019; Revised: 28.02.2020; Accepted:
 Journal of The Association of Physicians of India ■ Vol. 68 ■ August 2020 69

Table 1: Relation of HOMA-IR with CD4 counts a BD FACS Count system. Homeostatic
CD4 Count No. of CD4 Counts HOMA-IR t-value p-value
Model Assessment of Insulin Resistance
groups(cells/μl) Patients Mean SD Mean SD
(HOMA-IR) is used as a mathematical
Below 200 15 156.00 45.74 3.64 3.16 12.868 0.0001
model to measure IR. 7
200 - 350 27 280.25 39.23 1.23 1.12 36.941 0.0001 IR = Fasting Plasma Insulin(mU/L) x
Above 350 42 461.57 79.43 0.60 0.35 37.608 0.0001 FPG(mmol/L)/22.5
Total 84 HOMA-IR >2.5 was taken as cut-off
500 4 for IR. In order to assess the glycemic
status cut-off values for FPG were <100
450 3.5 mg/dl for normal glucose tolerance,
400 100-125 mg/dl for IFG & ≥126 mg/dl for
3 DM. For A1C, <5.6% for normal glucose
350 tolerance, 5.7-6.4% and ≥6.5% for IGT
CD4 Count (Cells/µl)

2.5 and DM respectively.

300

HOMA-IR
Serum Testosterone (TT), Follical
250 2 Stimulating Hormone (FSH) and
Leutinising Hormone (LH) estimation
200 1.5 was done on a fasting venous sample
150 using chemiluminescence assay. Serum
1 TT level less than 241.0 ng/dl was taken
100 as hypogonadism. Normal Serum TT,
50 0.5 FSH and LH levels were 241.0-827.0 ng/
dl, 1.4-18.1mIU/mL and 1.5-9.3 mIU/mL
0 0 respectively.
Below 200 200 - 350 Above 350 Serum LH and FSH levels were
used to classify patients into following
CD4 Count (Cells/µl) HOMA-IR categories:
Fig 1: Relation of HOMA-IR with CD4 counts 1 Eugonadism- normal TT and
normal LH and FSH,
Table 2: Relation of FPG with CD4 counts
2 Compensated hypogonadism-
CD4 groups No. of CD4 Counts FPG(mg/dl) t-value p-value normal TT and high LH and/or FSH
Cells/μl Patients Mean SD Mean SD
3 Secondary hypogonadism- low TT
Below 200 15 156.00 45.74 141.87 72.24 0.640 0.5273
and low or normal LH and/or FSH
200 – 350 27 280.25 39.23 89.70 15.09 23.556 0.0001
Above 350 42 461.57 79.43 75.52 7.18 31.368 0.0001 4 Primary hypogonadism-- low TT
Total 84 and high LH and /or FSH
500 160 Whole body BMD-DEXA (Bone
Mineral Density-Dual Energy X-ray
450 140 Absorptiometry) was used to measure
400 total body fat and its percentageregional
120 distribution over different areas of
350
CD4 Count (Cells/µl)

body namely arms, legs, trunk, android

300 100 and gynoid regions. Lunar Prodigy
FPG (mg/dl)

Advance machine (USA) was used to

250 80 calculate BMD. Percentage distribution
200 of fat in android (waist) region reflected
60
central obesity.
150
40 Statistical Analysis
100 Software used was IBM SPSS 20.1
50 20 and Microsoft Excel 2013 for analysis
of data. Mean and standard deviation
0 0 were calculated. The numerical data
Below 200 200 - 350 Above 350 was compared using two tailed student
t-test. The level of significance was
CD4 Count (Cells/µl) FPG(mg/dl)
considered 0.05. Log transformation
Fig. 2: Relation of FPG with CD4 counts was used for the conversion of
qualitative data (% android fat) to
from all HIV-infected patients for AIDS Control Organization of India quantitative data so that it can be
lymphocyte typing to obtain the CD4 (NACO) to Anti-Retroviral Therapy correlated to HOMA-IR using r-test.
cell count. The CD4 count was done (ART) Centre. CD4 count was done for The research work was approved by
using kits supplied by the National all patients using flow cytometry using ethical clearance committee.
 70 Journal of The Association of Physicians of India ■ Vol. 68 ■ August 2020

Table 3: Relation of A1C with CD4 counts cases were males with age ranging
CD4 Count No. of CD4 Counts A1C t-value p-value
from 21 to 68 years (mean= 42.3±10.5)
groups(cells/µl) Patients Mean SD Mean SD
years. The CD4 count amongst cases
Below 200 15 156.00 45.74 7.07 1.92 12.597 0.0001
ranged from 68cells/µl to 667cells/
200 - 350 27 280.25 39.23 5.47 0.75 36.388 0.0001 µl (mean=348.7±136.5).22 (26.2%) had
Above 350 42 461.57 79.43 4.70 0.28 37.274 0.0001 IR(HOMA-IR >2.5).19 (23%) cases had
Total 84 dysglycemia (FPG≥100). Out of these 19
cases, 11(13.1%) had IFG and 8 (9.5%)
500 8 had DM. 20 cases had A1C>5.6. That is
450 7 20 (24%) cases had dysglycemia, 9 had
IGT and 11 cases had DM. On the basis
400
6 of both FPG & A1C, 21(25%) patients
CD4 Count (Cells/µl)

350 had dysglycemia. 11 of them had DM

300 5 based on either FPG or A1C criteria.
Relation of HOMA-IR, FPG, & A1C

A1C
250 4
with CD4 counts is shown in Table 1
200 3 (Figure 1), Table 2 (Figure 2), and Table
150 3 (Figure 3) respectively. Patients with
2 lower CD4 counts had significantly
100 higher dysglycemia and IR.
50 1
33 (39 %) cases had hypogonadism,
0 0 six cases (7.14%) had primary
hypogonadism; 24 cases (28.57%)
Below 200 200 - 350 Above 350
had secondary hypogonadism & 3
cases (3.57 %) had compensatory
CD4 Count (Cells/µl) A1C
hypogonadism.
Fig 3: Relation of A1C with CD4 counts Relation of serum TT with CD4
Table 4: Relation of Serum TT with CD4 counts counts is shown in Table 4 (Figure
4). Serum testosterone levels were
CD4 Counts No. of cases CD 4 Counts TT level (ng/dl) t-value p-value
(cells/µl)
progressively lower (insignificant) with
Mean SD Mean SD
decreasing CD4 counts.
Below 200 15 156.00 45.74 167.38 87.18 0.448 0.658
200 - 350 27 280.25 39.23 248.93 84.96 1.740 0.088 In HOMA-IR group of ≤2.5,
Above 350 42 461.57 79.43 497.14 119.12 1.610 0.111 percentage android fat hat significant
Total 84 positive correlation with p-value=
0.001 & r-value= 0.405. Similarly, in
500 600 HOMA-IR group of >2.5, percentage
450 android fat had significant positive
500 correlation with p-value= 0.002 and
400
Testosterone level (ng/dl)

r-value= 0.626. As percentage android

CD4 Count (Cells/µl)

350 fat increases, IR increases (Table 5).

400
300 Discussion
250 300
The present study included 84 HIV
200 positive male patients. In a study by
200
150 Gazzaruso et al 8 133 out of 553 (24.0%)
cases showed high fasting glucose
100
100 o r we r e a l r e a d y o n a n t i - d i a b e t e s
50 treatment. In a study by Jerico et al 9
0 0 raised FPG, cut-off taken as ≥110mg/
dl, was present in 43% of the subjects.
Below 200 200 - 350 Above 350
In another study 10 on 755 HIV positive
males, DM was diagnosed in 34 subjects
CD4 Count (Cells/µl) TT level (ng/dl)
o u t o f 7 5 5 ( 4 . 5 % ) , w h i l e I F G wa s
Fig. 4: Relation of Serum TT with CD4 counts found in 71 (9.4%). Therefore, 13.9%
subjects showed a FPG concentration
Observations and Results investigations. Out of the remaining persistently above the normal value.
93 cases, nine cases were excluded Hyperinsulinemia was diagnosed in
A total of 111 HIV positive cases were from the study; 4 patients had chronic 86 out of 721 non-diabetic patients
recruited for the study. Out of 111 cases, kidney disease, 3 had hypothyroidism (11.9%). 34.2% HIV-patients on HAART
18 cases were dropped out of study & 2 had hyperprolactenemia. 84 cases showed IR using HOMA-IR in a study
as they were not willing for further were included in the study. All the by Guillen et al 3. Rosso et al 11found that

Table 5: Relation of HOMA-IR with percentage android fat
HOMA- HOMA-IR % ANDROID FAT
IR groups Mean SD Mean
≤2.5 0.75 0.46 19.48
>2.5 3.87 2.28 37.57
FPG was significantly lower in HIV-
infected patients than in control while
Fasting Plasma Insulin was significantly
higher in HIV-infected patients than in
controls. They calculated FGIR which
is a ratio of FPG and IR calculated
by HOMA-IR. IR (FGIR lower than 7
was taken as a cut-off value for IR)
was present in 26 out of 48 (52%)
HIV infected children. IR was twice
as much as compared to the present
study. However, FPG was significantly
lower in HIV- infected patients. Dada
et al 12 found that IR was present in
24.1% and 21.1% of HIV-infected
participants based on a HOMA-IR
and Quantitative Insulin Check Index
(QUICKI) respectively.
Dusingize 13 et al found that HIV
infection and more advanced HIV
infection (CD4 counts <200 cells/µL)
were associated with greater insulin
s e n s i t i v i t y i n a n t i r e t r o v i r a l n a ï ve
African women. Higher Resting Energy
Expenditure (REE) was a possible
explanation for such an observation.
D a v i e s e t a l . 14 f o u n d t h a t f o r e a c h
unit increase in log 10 viral load, A1C
increased 0.67 units (p= 0.0085).
Rochira et al 15 found that the mean
serum TT level in the population studied
was 452ng/dl which was significantly
lower than the normal population. In
another study conducted by Rietschel
et al 4, the mean serum TT levels were
found to be higher in HIV infected
male patients as compared to healthy
HIV uninfected controls. However, the
mean serum free TT levels were lower
for the HIV infected patients. This
discrepancy was attributed to increase
in SHBG levels among patients with
HIV. In the study by Rochira et al 15 the
prevalence of hypogonadism (serum
TT levels<300ng/dl) was 16%. 64.4%
of HIV infected males had serum TT
levels<300 ng/dl in a study conducted
by Robert Klein et al 16 . Jain et al 17
found the prevalence of hypogonadism
a m o n g H I V i n f e c t e d p a t i e n t s wa s
75.7%. Secondary hypogonadism
was found to be more common than
primary hypogonadism in a study by
Arver et al 18 (81% of all hypogonadal
HIV cases in a study conductedon 148
HIV infected males). Laudat et al 19
Journal of The Association of Physicians of India ■ Vol. 68 ■ August 2020
t-Value p-Value
SD
12.25 3.434 0.001
8.35 3.592 0.002
also showed that non-SHBG-bound
TT and DHT levels were correlated
with CD4 cell counts, showing that
hypogonadism occurs as the CD4
lymphocytes decrease. Reitschel et al 4
found no correlation between degree
of illness (CD4 cell count was used as
a marker of disease severity ) and TT
levels.
A s h a e t . a l 20 i n 2 0 1 2 f o u n d t h a t
HIV infected patients on ART had
significantly higher insulin resistance
and dyslipidemia in comparison
with ART-naïve patients. A greater
degree of IR was present in patients
with lipodystrophy in this study. In
present study also patients with greater
percentage android fat, i.e., greater
lipodystrophy had greater IR.
Thus; dysglycemia, IR and
hypogonadism are found to be highly
prevalent in HIV infected male patients.
So, it may be highly clinically relevant
to identify these disorders in the
HIV-infected population so that
appropriate interventions could be
taken up to improve the quality of life
in these patients, say, by improving
the hypogonadal symptoms and also
to reduce the overall complications
of diabetes especially cardiovascular
morbidity and mortality which has
upsurged in present era due to poor
glycemic status & insulin resistance
in these patients. Also early diagnosis
of IR could allow for appropriate
intervention and even prevent
progression to DM in many cases.
Limitations of study
The major limitation of the study
was that the duration and type of
ART was not taken into consideration.
Serum TT level was used as a measure
of hypogonadism instead of serum
free testosterone level that is a better
indicator of hypogonadism. Serum
SHBG levels were also not measured
that may have led to an underestimation
of hypogonadism in the HIV population
as SHBG levels are increased in HIV
infection leading to decreased levels
of free circulating testosterone in the
blood.
Conclusions
Dysglycemia, insulin resistance
71
and hypogonadism were found to be
r-Value
highly prevalent in HIV infected male
patients. Secondary hypogonadism
0.405
wa s m o r e c o m m o n t h a n p r i m a r y
0.626 hypogonadism among the HIV
population. Patients with lower CD4
counts had significantly higher insulin
resistance and dysglycemia. Serum
testosterone levels were progressively
lower (insignificant) with decreasing
CD4 counts.
Based on our results, we suggest
performing laboratory tests, such
as fasting glucose, OGTT, A1C and
serum TT during follow-up. The use
of HOMA-IR in these patients will
require further longitudinal studies
in order to demonstrate its usefulness
in early predicting diabetes or IGT in
this population. Given the uncertainty
about DHT effects on the bone and the
prostate, the advantages of using DHT
for androgen replacement or for its
effects in HIV infected men remain to
be demonstrated.
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