Chemical Senses, 2018, Vol 43, 59–64

doi:10.1093/chemse/bjx070
Original Article
Advance Access publication November 8, 2017

Original Article

The Association Between Diabetes and

Olfactory Function in Adults
Jason Ying Kuen Chan1, Esther García-Esquinas2, Owen H. Ko3,
Michael C. F. Tong1 and Sandra Y. Lin4
1
Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Shatin, N.T.,
Hong Kong SAR, 2Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma
de Madrid, Ciudad Universitaria de Cantoblanco, Ciber of Epidemiology and Public Health (CIBERESP), 28049 Madrid,
Spain, 3Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Ngan Shing Street,
Shatin, N.T., Hong Kong SAR and 4Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins Medical
Institutions, 601 N Caroline Street, Baltimore, MD 21287, USA

Correspondence to be sent to: Jason Chan, Department of Otorhinolaryngology, Head and Neck Surgery, Room 84026, 6/F Lui
Che Woo Clinical Sciences Building, Prince of Wales Hospital, Shatin, N.T., Hong Kong SAR. e-mail: jasonchan@ent.cuhk.edu.hk

Editorial Decision 1 November 2017.

Abstract
Diabetes is a significant chronic disease that in limited studies has been linked with olfactory
dysfunction. We investigated the cross-sectional association between diabetes and olfactory
dysfunction in 3151 adults aged ≥40 years who participated in US National Health and Nutrition
Examination Survey 2013–2014 with information on olfactory dysfunction and diabetes. Diabetes
was defined from fasting serum glucose ≥126  mg/dL, oral glucose tolerance test ≥200  mg/dL,
HbA1c levels ≥6.5%, physician-diagnosed diabetes, or current use of oral hypoglycemic agents
and/or insulin. Self-reported olfactory dysfunction was defined as a positive answer to any of the
following questions: 1)  “Have you had problem with smell in the past 12  months?”; 2)  “Have
you had a change in the ability to smell since age 25?”, or 3)  “Do you have phantom smells?”.
Participants were considered to have severe hyposmia or anosmia if they had <5 correct answers in
the 8-item pocket smell test. Analyses were adjusted for the main confounders, including olfactory
dysfunction risk factors. Compared to non-diabetics, diabetics under insulin treatment showed a
higher prevalence of phantom odors [OR(95% CI): 2.42 (1.16; 5.06)] and a non-significant higher
prevalence of severe hyposmia/anosmia [OR(95% CI): 1.57 (0.89; 2.78)]. Amongst diabetics, there
was a significant trend to severe hyposmia/anosmia for those on more aggressive treatments
[OR (95% CI) including oral and insulin treatment compared to those who reported no use of drug
treatment, respectively: 1.33 (0.60; 2.96) and 2.86 (1.28; 6.40); P trend 0.01]. No association was
observed between diabetes duration and prevalence of olfactory dysfunction.

Key words: diabetes, hyposmia, phantosmia, olfactory dysfunction

Introduction and equally as important, microvascular complications including

retinopathy, peripheral neuropathy, and renal disease (Manschot
Diabetes mellitus is a chronic disease that affects 14% of the US
et al. 2006; Candrilli et al. 2007; Tiehuis et al. 2010). These com-
population (Menke et al. 2015). Importantly, diabetes is associated
plications are a result of long standing poor glycemic control. The
with significant health-related complications including macrovascu-
management of diabetes and its associated complications, a disease
lar complications of heart disease, stroke, peripheral vascular disease,

© The Author(s) 2017. Published by Oxford University Press. All rights reserved.
59
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 60
that is of significant burden to both patients and society, is a pro-
cess that requires significant commitment from the patient including
lifestyle modifications, weight loss, and compliance with medication
(Inzucchi et al. 2015).
Olfactory dysfunction indicates abnormalities in the conduction
of olfactory stimuli externally to the olfactory epithelium or the sen-
sory pathways arising from the olfactory epithelium. Manifestations
of olfactory dysfunction may include phantosmia—the identifica-
tion of smells in the absence of an external stimuli, parosmia—the
identification of a smell that is incongruent with the external stimuli,
hyposmia—a diminished ability to detect and identify smells, and
anosmia—the inability to detect or identify smells. Amongst patients
with diabetes, data suggests that olfactory dysfunction, alterations of
the sensitivity of smell, may be a degenerative complication of diabe-
tes (Le Floch et al. 1993; Weinstock et al. 1993; Palouzier-Paulignan
et al. 2012; Varkonyi et al. 2014; Gouveri et al. 2014; Khil et al. 2015;
Mehdizadeh Seraj et al. 2015; Duda-Sobczak et al. 2017), secondary
to the effects of this disease on the central nervous system (Biessels
2013; Bruce et al. 2013). There may also be reduced olfactory function
in type 2 diabetics when compared with patients with type 1 diabe-
tes (Palouzier-Paulignan et al. 2012; Gouveri et al. 2014). If olfactory
dysfunction in diabetics does result from central nervous system dys-
function, similar to the cognitive impairment and depression noted in
diabetes (Biessels 2013; Bruce et al. 2013), this suggests that olfactory
testing may be helpful in the early recognition of diabetic complica-
tions (Brady et al. 2013; Gascon et al. 2013; Sanke et al. 2014).
Recently, the US National Health and Nutrition Examination
Survey (NHANES) included a smell component in the 2011–2014
chemosensory protocol using a standardized rapid smell assess-
ment and smell questionnaire, with the data from the 2013–2014
cycle readily available. A previous study of the NHANES has shown
increased risks for olfactory dysfunction dependent on age, eth-
nicity, socioeconomic status, education and alcohol consumption
(Hoffman et al. 2016). Here, the aim of this study was to evaluate
the association between diabetes and olfactory dysfunction in the US
general population using NHANES.
Methods
Study design and population
Between 2013 and 2014, the NHANES examined a US nationally
representative sample of 14 332 people by using a complex multi-
stage sample design. Of those selected, 10 175 completed an inter-
view. From these 10 175 participants, we excluded 6360 who were
younger than 40 years, 305 without complete information on olfac-
tory function, 147 with no information on diabetic status, and 212
with no information on potential confounders, leading to a sample
size of 3151 participants. The NHANES protocol was reviewed and
approved by the National Center for Health Statistics Institutional
Review Board. Written informed consent was given by the partici-
pants for their clinical records to be used in a research study.
Study variables
The study variables and names are available in Supplementary
Table 1.
Diabetes mellitus
Participants were considered diabetic if they had fasting serum glu-
cose ≥126 mg/dL, oral glucose tolerance test ≥200 mg/dL, measured
HbA1c levels ≥6.5%, self-reported diagnosis of diabetes, or cur-
rent use of oral hypoglycemic agents or insulin. Study participants
were categorized into 4 mutually exclusive groups: non-diabetics,
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Chemical Senses, 2018, Vol. 43, No. 1
diabetics who reported no use of oral hypoglycemic agents and/or
insulin, diabetics treated with blood glucose lowering drugs, and
diabetics treated with insulin regardless of their use of blood glucose
lowering drugs. Participants with self-reported diagnosed diabetes
were asked the age when first told they had diabetes.
Olfactory dysfunction
Self-reported olfactory dysfunction was defined as a positive answer
to any of the following 3 questions: 1)  “Have you had problem
with smell in the past 12 months?”; 2) “Have you had a change in
the ability to smell since age 25?” and 3)  “Do you have phantom
smells?”( CDC 2013; Rawal et al. 2016)
The 8-item pocket smell test was used to evaluate for the presence of
anosmia or severe hyposmia (Sensonics International). The pocket smell
test has been shown to be sensitive in identifying moderate to severe
olfactory dysfunction and have good test–retest reliability (Rawal et al.
2015). According to this test, participants were considered to have
severe hyposmia or anosmia if they had less than 5 correct answers.
Sociodemographic variables, lifestyle, obesity, and reported
comorbidity
Sociodemographic variables included age, gender, ethnicity (non-
Hispanic White, non-Hispanic Black, Mexican American, Other),
and education level (< high school, high school or equivalent, > high
school). Participants were classified as never smokers if they had
not smoked ≥100 cigarettes during a lifetime, and as ever smokers
if they had done so but were not current smokers at the time of
the interview. Participants were asked about their previous history
of cardiovascular disease (congestive heart failure, coronary heart
disease, heart attack, stroke), hypertension, head, or face injury,
xerostomia (persistent dry mouth in past 12 months) and sinonasal
symptoms (persistent cold/flu/nasal congestion in past 12  months,
presence of 2 or more sinus infections). Hypertension was defined
as a systolic blood pressure ≥140 mmHg, a diastolic blood pressure
≥90 mmHg, or the current use of antihypertensive drugs. The body
mass index (BMI) was calculated as the weight in kg divided by the
square height in metres.
Statistics
All statistical analyses were performed in STATA version 11.2 sta-
tistical software (Stata Corp), using the survey (svy) command to
account for the complex sampling design and weights in NHANES.
The prevalence of olfactory dysfunction was calculated overall and
by sex, age, ethnicity, education, tobacco consumption, BMI, pres-
ence of sinonasal symptoms, xerostomia, previous history of head/
face injury, hypertension, or cardiovascular disease.
To evaluate the association between diabetes and olfactory dysfunc-
tion, odds ratios (OR) and 95% confidence intervals (95% CI) were
estimated using logistic regression. Three models were built. In the basic
model, we considered age, gender, and race. We then fitted 2 models
by progressively adding: 1)  potential confounders of the association
between diabetes and olfactory dysfunction (educational level, smoking
status, presence of sinonasal symptoms, xerostomia, previous history of
head, or face injury); and 2) potential mediators of diabetes microvascu-
lar and macrovascular complications (hypertension, obesity, and cardio-
vascular disease). In sensitivity analyses, we also adjusted for additional
sociodemographic factors (marital status, poverty to income ratio)
and cardio-metabolic biomarkers (high density lipoprotein (HDL) and
low density lipoprotein (LDL) cholesterol), with similar findings. The
association between diabetes duration and olfactory dysfunction was
assessed using logistic regression models with the same confounders as
mentioned above. Statistical significance was set at 2-sided P < 0.05.
 Chemical Senses, 2018, Vol. 43, No. 1 61

Results 100] / [2.98 – 1]. No association between diabetes and prevalence of

other self-reported measures of olfactory dysfunction was observed.
The weighted prevalence of self-reported and measured olfac-
However, participants under insulin treatment did show a non-
tory dysfunction in the US population were 21.5% and 13.1%,
significant increased prevalence of severe hyposmia/anosmia (OR:
respectively. Individuals with self-reported olfactory dysfunction
1.68 (95% CI: 0.96; 3.00); Model 2, Table 1) when compared with
were more likely to be smokers, obese, have a history of head/face
non-diabetics.
injury, xerostomia, sinonasal symptoms, or cardiovascular disease.
Amongst diabetics (Table  2), there was a significant trend to
Individuals with measured olfactory dysfunction were more likely to
severe hyposmia/anosmia for those on more aggressive treatments
be male, older, non-white, <high school education, have xerostomia,
[ORs (95% CI) for participants on oral or insulin treatment com-
hypertension, and cardiovascular disease (Supplementary Table 2).
pared to those who reported no use of drug treatment were, respect-
In fully adjusted models for sociodemographic, lifestyle, and
ively, 1.30 (0.59; 2.90) and 2.87 (1.26; 6.52); P trend 0.01]. The
olfactory dysfunction risk factors, diabetics who used insulin
increased prevalence of hyposmia/anosmia among those with dia-
showed a higher prevalence of phantom odors than non-diabetics
betes was not explained by the increased prevalence of obesity,
[OR: 2.98 (95% CI: 1.41; 6.32); Model 2, Table 1)]. This associa-
hypertension, and cardiovascular disease observed among diabetics
tion was attenuated after further adjusting for potential mediators
(the change in the OR after adjustment for these factors was only
(BMI; hypertension and cardiovascular disease) [OR: 2.42 (95% CI:
of 0.5% [(1.30– 1.33) ×  100]/[1.30–  1]), or by an increased dur-
1.16; 5.06; Model 3, Table  1]; in particular, adjustment for these
ation of diabetes among those under more aggressive treatments (no
factors yielded a 28.3% reduction in the odds ratio [(2.98 – 2.42) × 

Table 1.  Odds ratios and 95% confidence intervals for the association between diabetes and olfactory dysfunction

n/total Model 1 odds Model 2 odds Model 3 odds

ratio (95% CI) ratio (95% CI) ratio (95% CI)

Problems with smell during last 12 months 245/3151

Diabetes
 Non-diabetics 178/2494 1.00 1.00 1.00
  Diabetics, treatment with no drugs 19/142 1.30 (0.66; 2.56) 1.22 (0.56;2.67) 1.09 (0.48; 2.48)
  Diabetics, oral medication 26/348 0.79 (0.42; 1.46) 0.62 (0.33; 1.16) 0.56 (0.31; 1.01)
  Diabetics, insulin medication 22/167 1.48 (0.73; 2.99) 1.20 (0.61; 2.37) 0.99 (0.48; 2.06)
  P-trend 0.63 0.54 0.20
Worsen ability to smell since age 25 449/3151
Diabetes
 Non-diabetics 346/2494 1.00 1.00 1.00
  Diabetics, treatment with no drugs 24/142 0.93 (0.56; 1.57) 0.88 (0.54; 1.45) 0.81 (0.51; 1.27)
  Diabetics, oral medication 51/348 1.18 (0.83; 1.67) 1.02 (0.65; 1.60) 0.94 (0.58; 1.54)
  Diabetics, insulin medication 28/167 0.93 (0.47; 1.84) 0.82 (0.40; 1.69) 0.71 (0.33; 1.53)
  P-trend 0.76 0.73 0.45
Phantom odour 228/3151
Diabetes
 Non-diabetics 161/2494 1.00 1.00 1.00
  Diabetics, treatment with no drugs 13/142 1.33 (0.57; 3.12) 1.12 (0.46; 2.73) 1.02 (0.44; 2.38)
  Diabetics, oral medication 34/348 1.56 (0.95; 2.55) 1.06 (0.59; 1.89) 1.00 (0.57; 1.77)
  Diabetics, insulin medication 20/167 3.92 (1.60; 9.60) 2.98 (1.41; 6.32) 2.42 (1.16; 5.06)
  P-trend <0.01 0.03 0.08
Self-reported olfactory dysfunctiona 634/3151
Diabetes
 Non-diabetics 483/2494 1.00 1.00 1.00
  Diabetics, treatment with no drugs 36/142 1.21 (0.82; 1.77) 1.09 (0.74; 1.62) 0.99 (0.68; 1.44)
  Diabetics, oral medication 72/348 1.18 (0.82; 1.71) 0.96 (0.60; 1.53) 0.86 (0.54; 1.38)
  Diabetics, insulin medication 43/167 1.53 (0.93; 2.52) 1.29 (0.86;1.94) 1.06 (0.69; 1.65)
  P-trend 0.08 0.56 0.76
Measured olfactory dysfunction (severe hyposmia/ 543/3151
anosmia)b
Diabetes
 Non-diabetics 397/2494 1.00 1.00 1.00
  Diabetics, treatment with no drugs 27/142 0.62 (0.33; 1.18) 0.60 (0.32; 1.12) 0.57 (0.30; 1.08)
  Diabetics, oral medication 63/348 0.85 (0.63; 1.15) 0.79 (0.59; 1.09) 0.77 (0.57; 1.05)
  Diabetics, insulin medication 56/167 1.99 (1.13; 3.48) 1.68 (0.96; 3.00) 1.57 (0.89; 2.78)
  P-trend 0.15 0.49 0.69

Model 1: Logistic regression model adjusted for age (continuous), gender, and race. Model 2: As model 1 and additionally adjusted for educational level, smok-
ing status, sinonasal symptoms, xerostomia, and previous history of head or face injury. Model 3: As model 2 and additionally adjusted for potential mediators:
BMI, hypertension and cardiovascular disease. CI, confidence interval.
a
Self-reported olfactory dysfunction was defined as a positive answer to any of the following questions: 1) Have you had problem with smell in the past
12 months?; 2) Have you had a change in the ability to smell since age 25? or; 3) Do you have phantom smells?
b
Measured olfactory dysfunction (presence of severe hyposmia or anosmia) was defined as having less than 5 correct answers in the 8 item pocket smell test.

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Table 2.  Odds ratios and 95% confidence intervals for the association between diabetes treatment and olfactory dysfunction

n/total Model 1 odds Model 2 odds Model 3 odds

ratio (95% CI) ratio (95% CI) ratio (95% CI)

Problems with smell during last 12 months 67/657

Diabetes
  Diabetics, treatment with no drugs 19/142 1.00 1.00 1.00
  Diabetics, oral medication 26/348 0.56 (0.35; 0.89) 0.50 (0.30; 0.85) 0.56 (0.33; 0.95)
  Diabetics, insulin medication 22/167 1.11 (0.33; 3.70) 0.98 (0.28; 3.52) 1.03 (0.30; 3.56)
  P-trend 0.84 0.97 0.94
Worsen ability to smell since age 25 103/657
Diabetes
  Diabetics, treatment with no drugs 24/142 1.00 1.00 1.00
  Diabetics, oral medication 51/348 1.22 (0.62; 2.42) 1.17 (0.54; 2.53) 1.23 (0.63; 2.38)
  Diabetics, insulin medication 28/167 1.01 (0.36; 2.79) 0.98 (0.34; 2.79) 0.85 (0.30; 2.45)
  P-trend 0.99 0.96 0.75
Phantom odour 67/657
Diabetes
  Diabetics, treatment with no drugs 13/142 1.00 1.00 1.00
  Diabetics, oral medication 34/348 1.24 (0.59; 2.61) 0.97 (0.48; 1.98) 1.11 (0.51; 2.45)
  Diabetics, insulin medication 20/167 3.18 (0.91; 11.20) 2.51 (0.88; 7.15) 2.18 (0.78; 6.10)
  P-trend 0.08 0.09 0.13
Self-reported olfactory dysfunctiona 151/657
Diabetes
  Diabetics, treatment with no drugs 36/142 1.00 1.00 1.00
  Diabetics, oral medication 72/348 0.97 (0.58; 1.68) 0.91 (0.49; 1.70) 0.94 (0.54; 1.64)
  Diabetics, insulin medication 43/167 1.32 (0.60; 2.91) 1.20 (0.56; 2.55) 1.06 (0.51; 2.20)
  P-trend 0.47 0.61 0.86
Measured olfactory dysfunction (severe hyposmia/ 146/657
anosmia)b
Diabetes
  Diabetics, treatment with no drugs 27/142 1.00 1.00 1.00
  Diabetics, oral medication 63/348 1.28 (0.60; 2.72) 1.30 (0.59; 2.90) 1.33 (0.60; 2.96)
  Diabetics, insulin medication 56/167 2.97 (1.46; 6.04) 2.87 (1.26; 6.52) 2.86 (1.28; 6.40)
  P-trend <0.01 0.01 0.01

Model 1: Logistic regression model adjusted for age (continuous), gender, race, and duration of diabetes. Model 2: As model 1 and additionally adjusted for
educational level, smoking status, sinonasal symptoms, xerostomia, and previous history of head or face injury. Model 3: As model 2 and additionally adjusted for
potential mediators: BMI, hypertension and cardiovascular disease. CI, confidence interval.
a
Self-reported olfactory dysfunction was defined as a positive answer to any of the following questions: 1) Have you had problem with smell in the past
12 months?; 2) Have you had a change in the ability to smell since age 25? or; 3) Do you have phantom smells?
b
Measured olfactory dysfunction (presence of hyposmia or anosmia) was defined as having less than 5 correct answers in the 8-item pocket smell test.

association observed between diabetes duration and prevalence of
hyposmia/anosmia as shown in Supplementary Table 3).
In sensitivity analyses, additional adjustments for race, poverty
income ratio, total serum cholesterol or serum high-density lipopro-
tein cholesterol, did not substantially change our results (data not
shown in tables).
Discussion
To our knowledge, this is the first nationally representative study to
evaluate the association between diabetes and olfactory function in
the United States. Results suggest that, compared to non-diabetics,
diabetics on insulin medication have a higher prevalence of phantom
odors, severe hyposmia, and anosmia. Additionally, they show that,
amongst diabetics, there is a significant trend to severe hyposmia and
anosmia for those on more aggressive treatments. However, they do
not suggest an association between duration of diabetes and devel-
opment of olfactory dysfunction.
Several mechanisms may explain the observed associations. First,
hyperglycaemia has been shown to result in increased cortical thin-
ning of the orbitofrontal cortex, and type 2 diabetes has shown to
be associated with significant atrophy of cortical and subcortical
regions of the brain, accelerated cognitive decline (McCrimmon
et al. 2012; Musen et al. 2012), and neural connectivity abnormali-
ties (Cui et al. 2015). Phantosmia is thought to be related to reduced
grey-matter volume at the insular cortex, cingulate cortex, hippo-
campus, and orbitofrontal cortex (Bitter et  al. 2011), and so dia-
betes could increase its risk by also affecting the orbitofrontal cortex
(Ajilore et al. 2010). Second, macrovascular disease may explain the
increased prevalence of severe olfactory dysfunction. In this sense,
controlling for cardiovascular disease and hypertension attenuated
the effect of diabetes on phantosmia. However, macrovascular dis-
ease did not explain the increased risk of severe olfactory dysfunction
noted in diabetics. Third, insulin resistance in the olfactory bulb and
orbitofrontal cortex potentially could also play a role in olfactory
dysfunction (De Felice et  al. 2014). In this sense, there is evidence
that insulin regulates the olfactory mucosa physiology (Lacroix et al.
2008) and that intranasal insulin may improve olfactory sensitiv-
ity and discrimination (Schopf et al. 2015). This third mechanism is
supported by the fact that the odds of severe olfactory dysfunction
was more likely in diabetics on insulin as opposed to those treated
conservatively or oral medication.

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 Chemical Senses, 2018, Vol. 43, No. 1
In regards to the association between type 2 diabetes mellitus with
cognitive impairment and dementia (Biessels et  al. 2006), olfactory
dysfunction has been demonstrated to predate clinical manifestations
of cognitive impairment or Alzheimer’s disease and may be an early
marker of the development of cognitive impairment (Serby et al. 1991;
Mesholam et al. 1998). Furthermore, olfactory dysfunction and cogni-
tive impairment in elderly patients with type 2 diabetes mellitus has
been shown to be associated (Sanke et al. 2014). With our current find-
ings of olfactory dysfunction amongst diabetics in a large population
based database, further investigation about cognitive impairment in
this group is warranted when cognitive function data becomes avail-
able on the NHANES database. These findings also suggest that evalu-
ating olfactory dysfunction in diabetic patients may have a potential in
predicting the development of cognitive impairment amongst diabetics.
Limitations of the current study may include residual confound-
ing by unmeasured factors unaccounted for in our analyses that may
underlie the observed associations. In this sense, for example, we
could not adjust for important risk factors of diabetes such as physi-
cal inactivity or total calorie intake due to a large number of missing
data. The cross-sectional study design precludes our ability to deter-
mine temporality or causation. The pocket smell test utilized in the
NHANES may not be truly reflective of the degree of olfactory dys-
function as compared to a more extensive test such as the Sniffin’ Stick
or University of Pennsylvania Smell Identification Test smell test. The
NHANES interview data are based on self-reports and may be subject
to misunderstanding of the questions or recall bias. We were also not
able to distinguish between adults with type 1 and type 2 diabetes.
However, previous work has demonstrated that type 2 diabetes is the
more predominant and likely representative of US adults (Cowie et al.
2009; Roy and Lloyd 2012). The NHANES dataset from the 2013–
2014 cycle also did not allow for the identification of patients with
microvascular complications from diabetes. The NHANES results are
limited to the US civilian household non-institutionalized adult popu-
lation and may not completely represent the US population. Finally,
NHANES data may not be completely reflective of actual clinical
practice, and the risk of diabetes in clinical populations may differ.
Despite these methodological limitations, the results of our study
provide the only population based estimates of self-reported and
measured olfactory dysfunction amongst adults with diabetes in the
US which will be valuable for future developments in the diagnosis
and monitoring of diabetic complications. The objective assessment
of olfactory dysfunction as opposed to self-reported information
alone and the size of the diabetic population examined support the
associations that have been identified in this study.
In conclusion, the results suggest that diabetes may be associ-
ated with olfactory dysfunction, in particular with the appearance of
phantom odors, severe hyposmia, or anosmia. This information may
be useful both for the diagnosis and monitoring of disease control
amongst diabetics and warrants further investigations of the mecha-
nisms involved.
Supplementary material
Supplementary data are available at Chemical Senses online.
Acknowledgements
J.C.  developed the idea, researched data, and wrote the manuscript.
E.G. researched data, wrote the manuscript, reviewed/edited the manuscript.
O.H., M.T., and S.L.  contributed to the discussion and reviewed/edited the
manuscript. This research was supported by the Dr Stanley Ho Medical
Foundation.
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63
Funding
This research was supported by the Dr Stanley Ho Medical Foundation. This
is in the form of a donation (project no. 6904215).
Conflict of interest
There are no conflicts of interest
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