Obstructive Sleep Apnoea, Glucose Tolerance and Liver ...

The Journal of International Medical Research
2007; 35: 458 – 466

Obstructive Sleep Apnoea, Glucose
Tolerance and Liver Steatosis in Obese

Women

G ACARTÜRK1, M ÜNLÜ2, S YÜKSEL1, R ALBAYRAK3, T KÖKEN4 AND Y PEKER5

1Department of Internal Medicine, 2Sleep Laboratory, Department of Chest Diseases,
3Department of Radiology, and 4Department of Clinical Chemistry, Afyon Kocatepe

University Hospital, Turkey; 5Sleep Medicine Unit, Department of Neurology and
Rehabilitation Medicine, Skaraborg Hospital, Skövde, Sweden

In this study of obstructive sleep apnoea there was a positive linear relationship
(OSA), glucose tolerance and liver between AHI and post-load glucose levels.
steatosis in females from an obesity unit, On multivariate logistic regression
45 patients (mean age 46.8 years, mean analysis, IGT was predicted by OSA
body mass index 39.4 kg/m2, all non- independently of age, waist circumference,
diabetic and alcohol abstainers) underwent systolic blood pressure and current
nocturnal polysomnography, a 2 h oral smoking. Liver steatosis was present in 37
glucose tolerance test and abdominal women (82.2%), of whom six had grade III
ultrasonography. OSA, defined as an steatosis. Of the variables tested, IGT was
apnoea–hypopnoea index (AHI) of ≥ 10 the only predictor of grade III steatosis. In
events/h, was present in 20 patients (44%). conclusion, OSA is an independent
Impaired glucose tolerance (IGT) was predictor of IGT which, in turn, is
found in eight patients (40%) with OSA associated with severe liver steatosis in an
and three patients (12%) without OSA; obesity unit-based sample of women.

KEY WORDS: SLEEP APNOEA; IMPAIRED GLUCOSE TOLERANCE; LIVER STEATOSIS; OBESITY; HYPERTENSION

Introduction steatosis is common in subjects with insulin
resistance9 and DM.10 Obstructive sleep
Obesity is associated with increased apnoea (OSA) is a common condition
incidence of diabetes mellitus (DM) and affecting 1 – 4% of the general population
impaired glucose tolerance (IGT).1,2 and 25 – 35% of obese individuals.11 It has
Compared with the normoglycaemic been shown to be associated with abdominal
population, IGT is associated with a higher visceral fat accumulation and glucose
incidence of coronary artery disease,3 stroke4 metabolism12 and increases the risk of
and mortality.5 Obesity is also associated cardiovascular disease.13 Little is known,
with liver steatosis, which may lead to however, about the complex associations
serious liver disease and mortality.6 – 8 Liver

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G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

between OSA, glucose tolerance and liver had a systolic blood pressure ≥ 160 mmHg
steatosis in obesity. The aim of this study was and/or a diastolic blood pressure ≥ 95
to investigate the relationship between OSA, mmHg.14 Patients were defined as
glucose tolerance and liver steatosis in a postmenopausal when they had not
female obesity unit cohort, adjusting for menstruated for at least 1 year.
confounding factors such as age, waist
circumference, body mass index, systolic METABOLIC ASSESSMENT
blood pressure and menopausal status. After a 10 h overnight fast, venous blood
samples were drawn between 08.00 and
Patients and methods 10.00 to determine levels of liver enzymes,
glucose and insulin and the lipid profile.
PATIENTS Plasma alanine aminotransferase (ALT),
Women were recruited consecutively from aspartate aminotransferase (AST), alkaline
the Obesity Unit of the Department of phosphatase (ALP) and γ-glutamyl-
Internal Medicine at the University Hospital transferase (GGT) activities were assayed
of Afyon, Turkey from February 2004 to using a Synchron CX4-CE (Moduler Hitachi
December 2005. Patients with decompensated P-800, Roche Diagnostics, Indianapolis, IN,
cardiac or respiratory insufficiency, manifest USA) at 30 °C. Elevated liver enzymes were
diabetes mellitus, liver disease or defined as a serum ALT, AST, ALP or GGT
malignancy were excluded from the study. level higher than the upper limit of normal
The Ethics Committee of Afyon Kocatepe (41, 32, 276 and 49 IU/l, respectively).
University Medical Faculty approved the Fasting cholesterol, triglyceride and high
study protocol, and informed consent was density lipoprotein (HDL) cholesterol
obtained from all the participating patients. concentrations were measured using a
commercially available immunocolorimetric
PATIENT ASSESSMENT assay (Moduler Hitachi E-170, Roche
Medical history and smoking habits were Diagnostics), while the low density
evaluated using a self-administered lipoprotein (LDL) cholesterol level was
questionnaire. Body weight was measured to derived using the Friedwald equation.
the nearest 0.1 kg, and height was measured Fasting glucose was measured in whole
barefoot to the nearest 0.01 m. Body mass blood using a glucose oxidase based assay,
index (BMI) was calculated from the weight and insulin was quantified using a
(kg) divided by the height (m2). Waist commercially available radioimmunoassay
circumference was measured with a flexible (Moduler Hitachi E-170, Roche Diagnostics).
plastic tape midway between the lower rib
margin and the iliac crest in the standing A standard oral glucose tolerance test was
position. Blood pressure was measured in the performed as described by the World Health
right arm at the level of the heart using a Organization;15 glucose concentrations
sphygmomanometer (Erka® , Bad Tölz, were measured at baseline and at 2 h post-
Germany) between the hours of 08.00 and load. Normal glucose tolerance was defined
10.00 in the supine position after a 5 min as a fasting glucose level < 100 mg/dl
rest; it was recorded as the mean of three (5.6 mmol/l) and a 2 h post-load glucose
measurements taken at 1 min intervals. level < 140 mg/dl (7.8 mmol/l). Patients were
Hypertension was diagnosed if the patients classified as having IGT if the fasting plasma
were on antihypertensive drug treatment or glucose concentration was ≥ 100 mg/dl

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G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

(5.6 mmol/l) but < 126 mg/dl (7.0 mmol/l), OVERNIGHT SLEEP STUDIES
or the 2 h post-load glucose concentration An overnight sleep study was performed in
was ≥ 140 mg/dl (7.8 mmol/l) but < 200 mg/dl all patients using 18-channel poly-
(11.1 mmol/l). DM was diagnosed if the somnography (SleepScreen Pro®, Viasys
fasting plasma glucose value was ≥ 126 mg/dl Healthcare, Hoechberg, Germany), which
(7.0 mmol/l) or the 2 h post-load glucose included a standard montage of
value was ≥ 200 mg/dl (11.1 mmol/l);16 these electroencephalogram (EEG), electro-
patients were excluded from the data oculogram and electromyogram signals
analysis. For participants with non-diabetic together with pulse oximetry, respiratory
fasting glucose values, the homeostasis impedance and nasal airflow detected by
model assessment (HOMA) index was used oronasal thermistors. All sleep studies were
as a measure of insulin resistance.17 This was manually analysed using computer software
calculated from the product of the fasting by the same physician (M.Ü.), who was
glucose (mmol/l) and fasting insulin (µU/l) blinded to the patient’s other clinical and
divided by the constant 22.5. ultrasonography data. Sleep stages were
scored according to the standard criteria of
The metabolic syndrome was defined Rechtschaffen and Kales.20 Apnoeas were
according to the National Cholesterol defined as complete cessation of airflow for
Education Program (NCEP) criteria, that is at least 10 s. Hypopnoea was defined as
the presence of three or more of the following ≥ 50% reduction in airflow accompanied by
risk components: (i) waist circumference > 3% desaturation in the preceding 30 s and
> 88 cm; (ii) triglyceride levels ≥ 150 mg/dl; a reduction in chest wall movement. EEG
(iii) HDL cholesterol levels < 50 mg/dl; arousals were not required to make the
(iv) blood pressure ≥ 130/≥ 85 mmHg or diagnosis of a respiratory event. Data were
pharmacologically treated hypertension; expressed as the apnoea–hypopnoea index
and (v) fasting glucose levels ≥ 110 mg/dl.18 (AHI) based on the number of apnoeas and
hypopnoeas per hour slept, with an AHI
ASSESSMENT OF LIVER STEATOSIS ≥ 10 events/h indicating a positive OSA
The presence and severity of liver steatosis diagnosis.21 In parallel, the total number of
was determined using the results of significant oxygen desaturations (a drop in
abdominal ultrasonography; these were all oxygen saturation of at least 4% from the
assessed by the same physician (R.A.), who immediately preceding baseline) was scored
was blinded to any of the patient’s other and the oxygen desaturation index (ODI)
data. Steatosis was staged according to was calculated from the number of
Scatarige et al.19: stage I, enhanced significant desaturations per hour of sleep.
echogenicity of the parenchyma with
normal image of the vessels and the STATISTICAL ANALYSIS
diaphragm boundaries; stage II, higher Continuous variables were expressed as the
number of minor and diffuse echoes in the mean ± SD, and categorical variables as
parenchyma, poorer imaging of the vessels numbers and proportions (%). The unpaired
and the diaphragm boundaries; stage III, Student’s t-test or the Mann–Whitney U-test
significant number of diffuse echoes in the were used to compare continuous variables,
parenchyma and weak or absent imaging of and the χ2 or the Fisher’s exact test were used
the vessels, diaphragm and the distal part of to compare categorical variables between
the right lobe of the liver.

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G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

subgroups of obese women with or without pressure measurements. In the OSA group,
OSA. Correlations between variables were 11 of the 16 women with hypertension were
assessed by the Pearson or Spearman on antihypertensive treatment (mostly a
correlation test. Multiple logistic regression combination of a calcium-channel blocker
analysis was performed to test the predictive and an angiotensin-converting enzyme
value of clinical, polysomnographical and inhibitor, or an angiotensin II antagonist).
metabolic parameters, using IGT and grade Despite antihypertensive drug treatment, the
III liver steatosis as dependent variables. The systolic blood pressure was significantly
odds ratio (OR) and 95% confidence interval higher in the OSA group than in the non-
(CI) were calculated from regression OSA group (Table 1). The diastolic blood
coefficients. All statistical tests were two- pressure tended to be higher in the OSA
sided, and a P-value < 0.05 was considered to group but this difference was not statistically
be statistically significant. All analyses were significant.
performed using SPSS® version 11.5 for
Windows (SPSS Inc., Chicago, IL, USA). With regard to the polysomnographical
data, patients with OSA had a shorter total
Results sleep time and a lower proportion of REM
and slow wave sleep than non-OSA patients,
Forty-seven women were recruited to the but these differences were not statistically
study. All patients were alcohol abstainers significant (Table 1). The mean AHI and the
and were not regular users of hepatotoxic mean ODI, another indicator of OSA, were
drugs. None of them had undergone a sleep significantly higher in the OSA group than
study prior to recruitment. After exclusion of in the non-OSA group (Table 1).
two subjects with previously undetected DM,
45 women with a mean age of 46.8 years A total of 11 (22.4%) patients were shown
(range 27 – 68 years) and a mean BMI of to have IGT, the proportion being
39.4 kg/m2 (range 30.0 – 59.3 kg/m2) were significantly higher in the OSA group than
included in the final study population. in the non-OSA group (Table 1). When
analysing the post-load glucose levels, the
Of the 45 women in the study, 20 (44%) OSA group had significantly higher values
had OSA. As shown in Table 1, women with than the non-OSA group, but the fasting
OSA were older than women without OSA blood glucose, insulin, cholesterol and
and the proportion of postmenopausal triglyceride levels did not differ significantly
women was higher in the OSA group, but between the groups (Table 1). Only three
these differences were not statistically subjects were on lipid-lowering drug
significant. BMI, waist circumference and treatment (two in the OSA group and one in
the proportion of patients who were current the non-OSA group).
smokers or who had metabolic syndrome or
hypertension did not differ significantly When analysing the associations between
between the groups. In the non-OSA group, various continuous parameters, there was a
six women were on antihypertensive drug significant positive relationship between the
treatment (three receiving calcium-channel 2 h post-load glucose levels and the AHI as
blockers, two receiving angiotensin- well as the ODI (Fig. 1). No significant
converting enzyme inhibitors, one receiving correlations were found between the 2 h
an angiotensin II antagonist) and 10 women post-load glucose levels and other variables.
were defined as hypertensive based on blood In a multivariate logistic regression analysis,
IGT was significantly predicted by OSA (OR

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G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

TABLE 1:
Comparison of the anthropometric, clinical and polysomnographical characteristics of
women from an obesity unit with and without obstructive sleep apnoea (OSA)

Patients with OSA Patients without OSA

(n = 20) (n = 25) P-value

Age (years) 50.0 ± 8.5 44.3 ± 10.1 NSa
Body mass index (kg/m2) 39.9 ± 8.0 39.0 ± 6.2 NSa
Waist circumference (cm) 106.3 ± 9.8 106.1 ± 11.5 NSa
Menopause 14 (70.0%) 11 (44.0%) NSb
Current smoker NSc
Metabolic syndrome 1 (5.0%) 4 (16.0%) NSb
Hypertension 15 (75.0%) 19 (76.0%) NSb
Systolic blood pressure (mmHg) 16 (80.0%) 16 (64.0%) 0.024a
Diastolic blood pressure (mmHg) 151.0 ± 17.7 138.8 ± 17.2 NSa
Total sleep time (min) 94.0 ± 13.9 87.4 ± 14.7 NSa
REM sleep (%) 302.1 ± 66.7 338.2 ± 62.6 NSa
Slow wave sleep (%) 11.9 ± 9.1 15.3 ± 8.3 NSa
AHI (events/h) 9.9 ± 7.6 10.1 ± 8.3 < 0.001a
ODI (events/h) 29.0 ± 20.6 3.6 ± 3.1 < 0.001a
IGT 36.9 ± 22.9 9.4 ± 9.4 0.041c
Fasting blood glucose (mg/dl) NSd
2 h post-load glucose (mg/dl) 8 (40.0%) 3 (12.0%) 0.008d
Insulin (µU/ml) 98.9 ± 11.2 99.9 ± 11.7 NSa
HOMA-IR 136.9 ± 38.5 114.3 ± 43.2 NSa
HDL cholesterol (mg/dl) 18.9 ± 9.1 20.2 ± 9.1 NSa
LDL cholesterol (mg/dl) NSa
Triglycerides (mg/dl) 4.8 ± 2.7 4.9 ± 2.0 NSa
Alkaline phosphatase (IU/l) 48.1 ± 7.0 44.4 ± 10.2 NSa
ALT (IU/l) 124.5 ± 39.0 123.6 ± 26.9 NSa
AST (IU/l) 130.6 ± 51.4 165.1 ± 101.9 NSa
GGT (IU/l) 145.1 ± 95.1 164.8 ± 53.7 NSa
Liver steatosis 21.1 ± 5.3 22.8 ± 11.0 NSb
Grade III liver steatosis 19.7 ± 3.9 20.0 ± 5.9 NSc
24.0 ± 21.1 20.1 ± 8.5
15 (75.0%) 22 (88.0%)

4 (20.0%) 2 (8.0%)

Values are the mean ± SD, or number (%).
aStudent’s t test; bχ2; cFisher’s exact test; dMann–Witney U-test.
REM, rapid eye movement; AHI, apnoea–hypopnoea index; ODI, oxygen desaturation index; IGT, impaired
glucose tolerance; HOMA-IR, homeostasis model assessment index (indicating insulin resistance); HDL, high
density lipoprotein; LDL, low density lipoprotein; ALT, alanine aminotransferase; AST, aspartate
aminotransferase; GGT, γ-glutamyltransferase; NS, not significant.

7.35, 95% CI 1.24 – 43.45, P = 0.028) steatosis (Table 1). Of these six, only one had
independently of other confounding slightly increased plasma ALT and AST
variables such as age, waist circumference, levels, and one had a slightly increased GGT
systolic blood pressure and current smoking value. There were no significant differences
(Table 2). between the OSA and the non-OSA group
with regard to liver enzyme levels (Table 1).
Liver steatosis was present in a total of 37 In a multivariate logistic regression analysis,
women (82.2%), of whom six had grade III

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G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

A B

300 300
280 280
260 260
240 240
220 220
200 200
180 180
160 160
140 140
120 120
100 100

80 80
60 60

0 10 20 30 40 50 60 70 80 90 0 10 20 30 40 50 60 70 80 90
Apnoea–hypopnoea index (events/h) Oxygen desaturation index (events/h)
Post-load blood glucose (mg/dl)
Post-load blood glucose (mg/dl)

FIGURE 1: Correlations between the 2 h post-load glucose concentration and
indicators of obstructive sleep apnoea in women from an obesity unit: (A)
apnoea–hypopnoea index (r = 0.411, P = 0.005); (B) oxygen desaturation index (r =
0.308, P = 0.040)

TABLE 2:
Multivariate logistic regression analysis of the predictors of impaired glucose tolerance in
women from an obesity unit

Odds ratio 95% confidence interval P-value

Age 1.00 0.91 – 1.11 NS
Waist circumference 1.05 0.97 – 1.14 NS
Systolic blood pressure 0.28 0.04 – 2.02 NS
Current smoker 0.83 0.06 – 10.89 NS
Obstructive sleep apnoea 7.35 1.24 – 43.45 0.028

NS, not significant.

grade III steatosis was predicted by IGT (OR which are indicators of OSA. Moreover,
9.6, 95% CI 1.4 – 66.4, P = 0.021) after grade III steatosis was significantly
adjustment for confounding factors. associated with IGT independently of age,
BMI, waist circumference, OSA and
Discussion postmenopausal status in this sample of
women from an obesity unit.
The present study demonstrated an
independent relationship between OSA and The relationship between OSA and IGT
IGT as well as systolic blood pressure in obese has previously been investigated in many
women after adjustment for known studies, but these have mainly involved men
confounding factors. There was a significant or sleep clinic cohorts. In the present
positive linear relationship between post- investigation, all the subjects were recruited
load glucose levels and both AHI and ODI, from an obesity unit and the study addressed

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G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

the impact of OSA on glucose tolerance as a 2 h oral glucose tolerance test, and
well as on liver steatosis. The strength of this reported a significant relationship between
study is the homogeneity of the cohort OSA and IGT that was independent of age
regarding gender, the lack of confounding and obesity.
factors such as DM and alcohol
consumption, the inclusion of menopausal The severity of hypoxia, as reflected in the
status, the use of overnight ODI, has previously been shown to be an
polysomnography to assess sleep apnoea, important factor in the relationship between
and the use of abdominal ultrasonography OSA and IGT.26 In the study of Meslier et al.,27
to evaluate liver steatosis. AHI was the only polygraphic parameter
independently related to glucose–insulin
With regard to IGT, the present results metabolism on multiple linear regression
confirm some previous clinic-based studies analysis. In the present study, there was a
on smaller samples suggesting an significant linear relationship between the 2
independent relationship between OSA and h post-load glucose levels and both AHI and
abnormal glucose tolerance.22 – 24 In 18 obese ODI. As the majority of the women studied
patients, Tiihonen et al.22 found a were morbidly obese, it is possible that
relationship between insulin resistance nocturnal oxygen desaturations could be a
indices and ODI but not AHI. Vgontzas et consequence of the obesity–hypoventilation
al.23 found that fasting insulin and blood status per se, which might in part explain
glucose were higher in 14 obese patients with why the ODI values were higher than the
OSA than in 11 obese subjects without OSA, AHI values in this sample. The significant
although the relationship between OSA and relationship between OSA and systolic blood
fasting blood glucose and insulin was not pressure in this obese cohort might also
investigated in this small sample. In another reflect increased sympathetic activity28
study, Brooks et al.24 demonstrated an which, in turn, may also facilitate the
improvement in insulin responsiveness in development of IGT.
nine type 2 diabetic patients with OSA after
treatment with nasal continuous positive It is recognized that liver steatosis is
airway pressure, suggesting that OSA may associated with cirrhosis and liver failure as
affect glucose–insulin metabolism. In a well as mortality.6 – 8 Liver steatosis is
larger sample of 261 males referred for common in subjects with obesity,6 insulin
suspected OSA, Strohl et al.25 demonstrated a resistance,9 DM,10 dyslipidaemia29 and
significant relationship between fasting arterial hypertension,30 and has been
insulin and AHI, independently of BMI. An suggested to be more prevalent in
oral glucose tolerance test was not postmenopausal women.31 To our
performed, however, and a large number of knowledge, there have been only a few
cases of IGT could have been missed. In a reports regarding the impact of OSA on liver
community sample of 150 healthy but function.32,33 Chin et al.32 documented
mildly obese males, Punjabi et al.26 suggested abnormal serum aminotransferase levels in
that OSA was associated with IGT and 40 obese men with severe OSA. Following
insulin resistance, independently of obesity. treatment of the OSA with continuous
In a larger, consecutive, sleep clinic-based positive airway pressure, they reported an
sample of 595 male subjects, Meslier et al.27 improvement in these enzymes. Moreover, in
performed overnight polysomnography and another study from a sleep unit,33 the
prevalence of abnormal liver enzymes was

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G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

found to be 20% in the OSA population, and 0.1 – 0.6 risk of complications such as
reached 32% in subjects with severe OSA bleeding, pneumothorax and biliary
(defined as an AHI of at least 50 events/h). In peritonitis.37
the present study, the severity of liver
steatosis was investigated in a non-diabetic, In the obesity unit cohort in the present
non-alcoholic sample of obese women based study, liver steatosis was common, which
on abdominal ultrasonography. This was not unexpected. There was no
technique has a relatively high sensitivity correlation between the severity of liver
(82 – 94%), even though the reported range steatosis and OSA or AHI/ODI, although the
of specificity is relatively large (66 – 95%).34 total number of subjects studied was
This technique permits the diagnosis of liver probably too small adequately to reflect this
steatosis but evaluation of lipid content or association. The significant relationships
the degree of steatosis is qualitative rather between OSA and IGT on the one hand and
than quantitative.35 Histopathological between IGT and grade III steatosis on the
examination is rarely used for the other might be two additional mechanisms
confirmation of liver steatosis, although its to explain the increased cardiovascular and
role is crucial in diagnosing the development liver-related morbidity in obese people.
of alcoholic hepatitis or steatohepatitis.36 It
should be kept in mind that biopsy is an Conflicts of interest
invasive technique associated with a
No conflicts of interest were declared in
relation to this article.

• Received for publication 4 December 2006 • Accepted subject to revision 7 December 2006
• Revised accepted 25 May 2007

Copyright © 2007 Field House Publishing LLP

References 6 Andersen T, Christoffersen P, Gluud C: The liver
1 Skarfors ET, Selinus KI, Lithell HO: Risk factors
in consecutive patients with morbid obesity: a
for developing non-insulin dependent diabetes:
a 10 year follow up of men in Uppsala. BMJ clinical, morphological, and biochemical study.
1991; 303: 755 – 760.
2 Harris MI, Hadden WC, Knowler WC, et al: Int J Obes 1984; 8: 107 – 115.
Prevalence of diabetes and impaired glucose
tolerance and plasma glucose levels in US 7 Angulo P: Nonalcoholic fatty liver disease. N
population aged 24 – 74 yr. Diabetes 1987; 36:
523 – 534. Engl J Med 2002; 346: 1221 – 1231.
3 Blake DR, Meigs JB, Muller DC, et al: Impaired
glucose tolerance, but not impaired fasting 8 Teli MR, James OF, Burt AD, et al: The natural
glucose, is associated with increased levels of
coronary heart disease risk factors: results from history of nonalcoholic fatty liver: a follow-up
the Baltimore Longitudinal Study on Aging.
Diabetes 2004; 53: 2095 – 2100. study. Hepatology 1995; 22: 1714 – 1719.
4 Vermeer SE, Sandee W, Algra A, et al for the
Dutch TIA Trial Study Group: Impaired glucose 9 Reaven GM: Banting lecture 1988. Role of
tolerance increases stroke risk in nondiabetic
patients with transient ischemic attack or insulin resistance in human disease. Diabetes
minor ischemic stroke. Stroke 2006; 37: 1413 –
1417. 1988; 37: 1595 – 1607.
5 Saydah SH, Loria CM, Eberhardt MS, et al:
Subclinical states of glucose intolerance and 10 Gupte P, Amarapurkar D, Agal S, et al: Non-
risk of death in the US. Diabetes Care 2001; 24:
447 – 453. alcoholic steatohepatitis in type 2 diabetes

mellitus. J Gastroenterol Hepatol 2004; 19: 854 –

858.

11 Gami AS, Caples SM, Somers VK: Obesity and

obstructive sleep apnea. Endocrinol Metab Clin

North Am 2003; 32: 869 – 894.

12 Punjabi NM, Ahmed MM, Polotsky VY, et al:

Sleep-disordered breathing, glucose

intolerance, and insulin resistance. Respir

Physiol Neurobiol 2003; 136: 167 – 178.

13 Peker Y, Hedner J, Norum J, et al: Increased

incidence of cardiovascular disease in middle-

aged men with obstructive sleep apnea: a 7-

465Downloaded from imr.sagepub.com by guest on March 18, 2016

G Acartürk, M Ünlü, S Yüksel et al.
Obstructive sleep apnoea, glucose tolerance and liver steatosis in obese women

year follow-up. Am J Respir Crit Care Med 2002; on insulin responsiveness. J Clin Endocrinol
166: 159 – 165. Metab 1994; 79: 1681 – 1685.
14 Zanchetti A, Chalmers JP, Arakawa K, et al: The 25 Strohl KP, Novak RD, Singer W, et al: Insulin
1993 guidelines for the management of mild levels, blood pressure and sleep apnea. Sleep
hypertension: memorandum from a WHO/ISH 1994; 17: 614 – 618.
meeting. Blood Press 1993; 2: 86 – 100. 26 Punjabi NM, Sorkin JD, Katzel LI, et al: Sleep-
15 Alberti KG, Zimmet PZ: Definition, diagnosis disordered breathing and insulin resistance in
and classification of diabetes mellitus and its middle-aged and overweight men. Am J Respir
complications. Part 1: diagnosis and Crit Care Med 2002; 165: 677 – 682.
classification of diabetes mellitus – provisional 27 Meslier N, Gagnadoux F, Giraud P, et al:
report of a WHO consultation. Diabet Med 1998; Impaired glucose-insulin metabolism in males
15: 539 – 553. with obstructive sleep apnoea syndrome. Eur
16 American Diabetes Association: Diagnosis and Respir J 2003; 22: 156 – 160.
classification of diabetes mellitus. Diabetes Care 28 Somers VK, Dyken ME, Clary MP, et al:
2005; 28: S37 – S42. Sympathetic neural mechanisms in obstructive
17 Matthews DR, Hosker JP, Rudenski AS, et al: sleep apnea. J Clin Invest 1995; 96: 1897 – 1904.
Homeostasis model assessment: insulin 29 Assy N, Kaita K, Mymin D, et al: Fatty
resistance and beta-cell function from fasting infiltration of liver in hyperlipidemic patients.
plasma glucose and insulin concentrations in Dig Dis Sci 2000; 45: 1929 – 1934.
man. Diabetologia 1985; 28: 412 – 419. 30 Donati G, Stagni B, Piscaglia F, et al: Increased
18 Expert Panel on Detection, Evaluation, and prevalence of fatty liver in arterial hypertensive
Treatment of High Blood Cholesterol in Adults: patients with normal liver enzymes: role of
Executive Summary of the Third Report of the insulin resistance. Gut 2004; 53: 1020 – 1023.
National Cholesterol Education Program 31 Clark JM: The epidemiology of nonalcoholic
(NCEP) Expert Panel on Detection, Evaluation, fatty liver disease in adults. J Clin Gastroenterol
and Treatment of High Blood Cholesterol in 2006; 40(suppl 1): S5 – 10.
Adults (Adult Treatment Panel III). JAMA 2001; 32 Chin K, Nakamura T, Takahashi K, et al: Effects
285: 2486 – 2497. of obstructive sleep apnea syndrome on serum
19 Scatarige JC, Scott WW, Donovan PJ, et al: Fatty aminotransferase levels in obese patients. Am J
infiltration of the liver: ultrasonographic and Med 2003; 114: 370 – 376.
computed tomographic correlation. J 33 Tanne F, Gagnadoux F, Chazouilleres O, et al:
Ultrasound Med 1984; 3: 9 – 14. Chronic liver injury during obstructive sleep
20 Rechtschaffen A, Kales A: A Manual of apnea. Hepatology 2005; 41: 1290 – 1296.
Standardized Terminology, Techniques, and Scoring 34 Joseph AE, Saverymuttu SH, al-Sam S, et al:
System for Sleep Stages in Human Subjects. Los Comparison of liver histology with
Angeles: Brain Information Service, UCLA, ultrasonography in assessing diffuse
1968. parenchymal liver disease. Clin Radiol 1991; 43:
21 Lavie P, Herer P, Hoffstein V: Obstructive sleep 26 – 31.
apnoea syndrome as a risk factor for 35 Mendler MH, Bouillet P, Le Sidaner A, et al:
hypertension: population study. BMJ 2000; 320: Dual-energy CT in the diagnosis and
479 – 482. quantification of fatty liver: limited clinical
22 Tiihonen M, Partinen M, Narvanen S: The value in comparison to ultrasound scan and
severity of obstructive sleep apnoea is single-energy CT, with special reference to iron
associated with insulin resistance. J Sleep Res overload. J Hepatol 1998; 28: 785 – 794.
1993; 2: 56 – 61. 36 Graif M, Yanuka M, Baraz M, et al:
23 Vgontzas AN, Papanicolaou DA, Bixler EO, et Quantitative estimation of attenuation in
al: Sleep apnea and daytime sleepiness and ultrasound video images: correlation with
fatigue: relation to visceral obesity, insulin histology in diffuse liver disease. Invest Radiol
resistance, and hypercytokinemia. J Clin 2000; 35: 319 – 324.
Endocrinol Metab 2000; 85: 1151 – 1158. 37 Piccinino F, Sagnelli E, Pasquale G, et al:
24 Brooks B, Cistulli PA, Borkman M, et al: Complications following percutaneous liver
Obstructive sleep apnea in obese noninsulin- biopsy. A multicentre retrospective study on 68
dependent diabetic patients: effect of 276 biopsies. J Hepatol 1986; 2: 165 – 173.
continuous positive airway pressure treatment

Address for correspondence
Dr G Acartürk

Department of Internal Medicine, Afyon Kocatepe University Hospital, TR - 03200 Afyon,
Turkey.

E-mail: [email protected]

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