European Journal of Cardiovascular Medicine

Taste and smell may influence the acceptance or rejection of food, allowing to recognize chemical characteristics and nutritive substances of ingested food.^[1] Previous studies reported that the activation of sensory receptors induces oral and gastrointestinal secretion, contributing to the metabolic and digestive process.^[2] Recent findings also showed that ectopic taste and smell receptors could act directly in the regulation of gastrointestinal functions, insulin and glucagon secretion, sense of satiety, and gut motility.^[3]

Moreover, the literature suggests that sensory dysfunction, which influences food intake and body weight maintenance, might affect the risk of chronic diseases.^[4] Impairment of taste sensation and reduced gustatory function were observed in patients with type 2 diabetes (DM2). ^[5] A past work reported that approximately one-third of diabetic subjects present a reduced taste ability (hypogeusia), suggesting that this disorder could inhibit the ability to follow a controlled diet and consequently have good glycemic control. ^[6]

In another study, taste impairment was observed in 80% of uncontrolled diabetic patients and 50% of controlled patients, suggesting a link with glycemic level. More recently, a taste function reduction was observed in DM2 patients with good metabolic control and no signs of neuropathy, retinopathy, or nephropathy. Moreover, an association between sweet taste disorder in diabetes, high daily sugar intake, and vascular complications was also reported.^[7]

Regarding olfactory function, a high prevalence of smell impairment in diabetic subjects compared to the general population was observed.^[8] A study in an indiscernible sample of patients with type 1 and type 2 diabetes reported that this dysfunction was not associated with glycated haemoglobin (HbA1c) value, duration of diabetes, and micro- and macro-vascular events. ^[9] Conversely, Gouveri showed that type 2 diabetes was independently associated with olfactory dysfunction and that diabetic peripheral neuropathy and retinopathy were linked with severe smell impairment. Another study also found that smell impairment was correlated with the use of diabetic drugs, specifically insulin.

Several hypotheses on the relationship of taste and smell impairments with diabetes have been advanced. For example, the possible involvement of the reduction of salivary flow and zinc deficiency has been reported.^[10] The activation of taste cells by hyperleptinemia secondary to insulin resistance, impairment of brain plasticity within the olfactory system, and the presence of diabetes-related complications (e.g. neuropathy) may represent other involved mechanisms. However, it is still unclear if the impairment should be considered the cause of the pathology or a related complication, and the correlation between DM2 and taste or smell dysfunctions remains controversial.^[11] Moreover, to date, the vast majority of studies have focused only on taste or smell perception (not on both senses). Similarly, most of the literature considered only one or few related diabetes factors.

This was a cross-sectional study comprising a sample size of 80. Patients aged 25 to 50 years with T2DM < 5 years duration with HBA1C ≤ 7 were recruited from a tertiary care hospital for the research. They were divided into 2 groups, Group I- with normal weight (BMI of 18.5 to <25) and Group II with grade 1 obesity (BMI of 30 to < 35). The duration of the study was 2 months.

Exclusion criteria comprised of subjects with a past or present history of psychiatric disorders, recent respiratory tract infection, hypothyroidism, chronic kidney or liver disease stage, on sedatives, antibiotics, antiepileptic medications, alcoholics, smokers, pan, tobacco and other substance abusers, pregnant or breastfeeding women and subjects who have contacted COVID-19 in the past six months. Consent was obtained from the Institute’s Review Board. HBA1C levels, anthropometric measurements and BMI were calculated.

The triple drop test was used to evaluate gustatory function. Five different concentrations of sweet, salty, sour and bitter tastants were used in dilutions of 50% steps using sucrose, sodium chloride, citric acid, and quinine hydrochloride respectively. Samples were presented as drops on the anterior part of tongue, swished in the mouth for ~5 seconds and spit out. Subject was asked to rinse the mouth thoroughly with water in between. Scoring was done depending on the identification of concentrations, “1” being highest, “5” being the lowest concentration.

Statistical analysis

Quantitative variables were analysed using descriptive statistics such as mean and standard deviation, qualitative variables were analysed using frequency and percentage. Student’s t test was used to test the difference in the mean values. Data was collected and entered in Excel spreadsheet for statistical analysis. Free trial version of SPSS software was downloaded and used for statistical analysis. A p <0.05 was deemed as significant. The variables were not normally distributed in the 2 subgroups of the variable group. Thus, non-parametric tests were used to make group comparisons.

Study Population Of a total of 80 T2DM patients recruited, only 50 met the selection criteria and were enrolled for the study. The characteristics of the T2DM patients and 50 control subjects are described in Table 2. The two groups were similar for age, gender distribution, and body mass index (BMI), and differed only for fasting glucose values, as expected. Individual data for each type of stimulus are reported in Supplementary

Table 1. Baseline Characteristics of Participants (n=80)

Table 1 presents the baseline characteristics of the 80 obese type 2 diabetic individuals included in the study. The mean age was 55.4 ± 8.2 years, with 42 (52.5%) males and 38 (47.5%) females. The mean BMI was 33.8 ± 4.5 kg/m², and the average HbA1c level was 8.2 ± 1.4%.

Table 2. Comparison of Taste Sensitivity Scores between Groups

Table 2 compares taste sensitivity scores between obese type 2 diabetic individuals (n=80) and obese non-diabetic controls (n=40). Diabetic individuals exhibited significantly lower taste sensitivity across all taste modalities (p < 0.05).

Table 3. Correlation between Taste Sensitivity and Clinical Parameters

Pearson’s correlation analysis (Table 3) demonstrated a significant inverse relationship between taste sensitivity and HbA1c, BMI, and fasting blood glucose levels.

Table 4. Prevalence of Taste Dysfunction in Diabetic Individuals (n=80)

Table 4 shows the prevalence of taste dysfunction in the diabetic group. A higher proportion of individuals had dysfunction for bitter (72.5%) and sour (68.8%) tastes.

Table 5. QoL Scores in Diabetic Individuals With and Without Taste Dysfunction

Table 5 presents the comparison of quality of life (QoL) scores between diabetic individuals with and without taste dysfunction. Those with taste dysfunction reported significantly lower QoL scores (p < 0.05).

Diabetes is the most common cause of peripheral neuropathy. Distal symmetrical sensorimotor polyneuropathy is the most common form of diabetic neuropathy.^[12] Duration of diabetes and peripheral neuropathy had the strongest association with taste impairment.^[13] In this study, it was observed that taste threshold for sweet and salty taste was higher and statistically significant (P < 0.01) in Type 2 diabetic patients compared to their control. However, it was not significantly different for other taste modalities-sour, bitter, and umami.^[14]

These findings in the present study are well in agreement with the observations of the previous studies, conducted by many researchers. In a study conducted by Dey and Inamdar, it was revealed that there was significantly lowered tasting ability in the diabetic subjects for sweet, salt, sour, and bitter solutions as compared to the controls. Moreover, highly significant results were observed for sweet taste among the different sensations.^[15] Similarly, Gondivkar et al. conducted a study in diabetics and concluded with the findings that Type 2 diabetic patients had a blunted taste response for sweet followed by sour and then salt tastes. They pointed out that the taste abnormality may influence the choice of nutrients, with a preference for sweet-tasting foods, thereby exacerbating hyperglycemia.^[16]

Similar study by Gaphor and Saeed, for evaluation of taste sensation showed that diabetic patients have less sensitivity to sweet and salty taste than healthy individuals. There were no differences in sour and bitter sensation sensitivity between diabetic and non-diabetic healthy individuals. Furthermore, they pointed out that the age, sex, and duration of the disease had no effect on taste disturbance.^[17]

On the other hand, the present study was conducted in Type 2 diabetics, wherein the primary taste modality umami was also included, which was not considered previously by other researchers, who worked on taste threshold in Type 2 diabetics. Umami, the recently established fifth primary taste modality was included as a tastant. Kurihara and Kashiwayanagi conducted a study on umami taste, in which the canine taste system was sensitive to umami substance and showed a large synergism between monosodium glutamate and disodium guanylate or disodium inosinate. Single-fiber analysis on the responses of mouse glossopharyngeal nerve and monkey’s primary taste cortex neurons also showed that the responses to umami substances are independent of other basic tastes. On the basis of these results, it was proposed that the umami taste is fifth basic taste, and there is a unique receptor for umami substances^.[18]

The underlying cause for taste impairment in DM is unclear. However, the probable mechanism for the heightened taste thresholds in diabetes could be explained on the basis of a different school of thoughts. Taste impairment may be a degenerative complication of DM; due to neuropathy of the “taste nerves.”^[19] Increased intracellular glucose in diabetics leads to the formation of advanced glycosylation end products (AGEs), which bind to a cell surface receptor. AGEs have been shown to cross-link proteins (e.g., collagen and extracellular matrix proteins), accelerate atherosclerosis, promote glomerular dysfunction, reduce nitric oxide synthesis, induce endothelial dysfunction, and alter extracellular matrix composition and structure.^[20]  

Hyperglycemia increases glucose metabolism through the sorbitol pathway. Increased sorbitol concentration alters redox potential, increases cellular osmolality, generates reactive oxygen species, and likely leads to other types of cellular dysfunction. Hyperglycemia increases the formation of diacylglycerol leading to activation of protein kinase C (PKC). PKC alters the transcription of genes for extracellular matrix proteins in endothelial cells and neurons leading to complications such as neuropathy, retinopathy, and renal complications. Inherent or acquired defect of the taste receptor, or abnormality of the mechanism underlying the central appreciation of taste within the brain, or microangiopathy involving the taste buds may also be responsible for the taste impairment.^[21]

The other school of thought specifically points out toward a significant and specific impairment in glucose taste detection. It is said that in diabetics a taste abnormality for glucose might conceivably be due to a frequent elevation of the blood sugar (“satiation effect”).^[22,23]

Our study concludes that gustatory impairment for the tastants – sweet, salty, sour, and bitter was observed in obese Type 2 Diabetes mellitus patients having the disease for less than 5 years, though maintaining a fair glycaemic control. This may affect their choices of food items like preference for sweet- tasting food which can exacerbate hyperglycaemia and aggravate obesity. Hypoguesia may also lead to greater intake of salty diet which can escalate the risk of hypertension, renal and heart diseases. Obesity itself is a risk factor for many diseases especially in diabetic individuals and it should not progress further. Knowledge about Hypogeusia in obese diabetics may be used in dietary counseling.

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