Over the past few decades, the global prevalence of type 2 diabetes mellitus (T2DM) has increased markedly, with projections estimating up to 7,862 cases per 100,000 individuals [1]. This upward trend may be attributed to a complex interplay of genetic and environmental risk factors, including obesity, insulin resistance, metabolic dysfunction, dietary habits, and epigenetic modifications [1]. In addition to these well-established risk factors, emerging evidence suggests that behavioral psychology and impaired satiety signaling also play a significant role in the pathogenesis of T2DM [2–4].

Recent studies have identified that single nucleotide polymorphisms (SNPs) in taste genes are significantly associated with elevated risk of metabolic syndrome, diabetes mellitus, obesity, carcinogenesis, Alzheimer’s disease, Parkinson’s disease, thyroid dysfunction, and substance use disorders [3–5]. Taste perception and signal transduction across the six taste modalities—sweet, salt, sour, bitter, umami, and fat taste—are mediated by various taste receptor genes such as type 1 taste receptor gene family R (TAS1R), TAS2R, sodium channel epithelial 1 (SCNN1), cluster determinant 36 (CD36), transient receptor potential cation channel subfamily M gene (TRPM), guanine nucleotide binding protein subunit alpha transducing 3 (GNAT3), carbonic anhydrase VI gene (CA6), IZUMO sperm-egg fusion 1 gene (IZUMO1), metabotropic glutamate receptor 1 gene (GRM1), and polycystic kidney disease (PKD)-like genes (e.g., PKD1L3, PKD2L1, and PKD2L3) [4–7]. Each taste modality is regulated by specific taste receptor genes. For instance: sweet taste is primarily mediated by TAS1Rs, TRPMs, and GNAT3; bitter taste by TAS2Rs, TRPMs, and CA6; salt taste by transient receptor potential vanilloid-1 (TRPV1; nerve endings) and SCNN1s (subunits alpha, beta, gamma, and delta); sour taste by TAS1Rs and PKD-like genes; umami taste by TAS1Rs, TRPMs, GNAT3, and GRM1; and fat taste by CD36 and IZUMO1 [5–7]. Taste perception begins with the interaction of food containing particular taste stimuli with oral and extra-oral taste receptors, triggering intracellular calcium release into the cytoplasm, depolarization of afferent nerve fibers and signal transduction via cranial nerves (facial nerve, glossopharyngeal nerve, sensory vagal afferents, trigeminal nerve and the trigeminal ganglion) to the central processing centers (nucleus of solitary tract, ventral posteromedial thalamic nucleus, the operculum, insular and the somatosensory cortex) [8]. These brain regions also influence gut hormone secretion [e.g., ghrelin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulin-releasing peptide], thereby regulating satiety and energy homeostasis [8]. Genetic variations in taste receptors may impair this signaling cascade, leading to altered taste perception, eating behavior, impaired energy homeostasis, and increased susceptibility to T2DM [5]. Notably, TAS1R expression in the gut is upregulated in response to hyperglycemia in individuals with T2DM [9]. This suggests that modulating taste receptor pathways may have therapeutic potential, particularly through agents that mimic GLP-1 receptor agonists [2, 8].

Several studies have reported significant taste impairments in individuals with diabetes mellitus [10, 11]. Chamoun et al. [12] demonstrated associations between psychophysical measures of taste and 94 SNPs across 11 taste receptor genes, particularly those related to sweet, salty, umami, and fat taste perception. A recent review further highlighted the critical role of taste receptor function in the pathophysiology of T2DM and energy homeostasis [13].

Despite the growing body of evidence, no qualitative meta-synthesis has systematically evaluated the association between SNPs in taste receptor genes and T2DM. This study aims to evaluate the evidence on the association of taste gene polymorphisms and T2DM.

This qualitative meta-synthesis was registered with the International Prospective Register of Systematic Reviews (PROSPERO; Registration No. CRD42022351880) [14] and conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines.

The PRISMA flowchart (Figure 1) illustrates the selection process. A total of 5,712 records were identified through database searches and manual screening. After title and abstract screening, followed by full-text review, sixteen studies met the eligibility criteria and were included in the qualitative meta-synthesis. Four studies were excluded due to the inclusion of populations other than T2DM (one study was conducted in individuals with prediabetes [15], and three studies were conducted in patients with gestational diabetes mellitus (GDM) [16–18]).

The characteristics of the included studies were summarized in Table 1 and Table S1. Diagnostic criteria for T2DM were based on the definitions used within each included study. Methodological quality assessment of the included studies by the Newcastle-Ottawa scale indicated that all sixteen studies were of good quality (Table S1).

The results revealed that SNPs in taste genes including TAS2R3 gene (SNP rs11763979), TAS2R4 gene (SNP rs2233998), TAS2R7 gene (SNPs rs2588350 and rs619381), TAS2R9 gene (SNP rs3741845), TAS2R38, TAS2R50 gene (SNP rs6488334), TRPV1 gene (SNPs rs161364 and rs8065080), CD36 gene (SNPs rs1761667, rs3211956, rs7755, rs1049673, and rs1527479), and CA6 gene (SNP rs2274327) were significantly associated with patients with T2DM. Additionally, TRPM5 gene (SNP rs4929982) and TRPM8 gene (SNP rs12472151) polymorphisms were significantly associated with metabolic syndrome, including T2DM.

The findings suggest that SNPs in several taste-related genes, including TAS2R3, TAS2R4, TAS2R7, TAS2R9, TAS2R38, TAS2R50, TRPV1, CD36, CA6, TRPM5, and TRPM8, may contribute to the etiology of T2DM and its associated metabolic complications. Although the precise mechanisms remain to be elucidated, current evidence supports the hypothesis that genetic variations in taste genes influence taste stimuli perception, individual food preferences, nutrient intake, and eating behavior, thereby increasing the risk of T2DM [22].

For instance, TAS2R9 is expressed in gut entero-endocrine L-cells and mediates GLP-1 secretion in response to sweet taste stimuli [22]. Canivenc-Lavier et al. [13] recently described local glucose-dependent GLP-1 secretion by taste bud cells and proposed taste receptors as potential targets for T2DM treatment [3]. Similarly, reduced CD36 expression due to genetic polymorphisms may influence fat taste sensitivity and intake behaviors, possibly exerting a protective effect due to reduced fat taste sensitivity [4, 33]. Variations in the TRPM5 gene are associated with reduced GLP-1 levels, impaired insulin release, and altered glucose tolerance, highlighting the metabolic relevance of taste receptor polymorphisms [3, 22].

This is in line with previous observations that the taste-dependent manner of GLP-1 secretion, glucose-stimulated insulin secretion, and insulin sensitivity in patients with T2DM might be associated with the polymorphisms in taste receptor genes [3, 22, 26, 33]. These genetic variations may affect hunger signaling, gut motility, and taste-driven satiety hormone release [3, 4, 13]. For example, individuals carrying the TAS2R38 proline-alanine-valine (PAV) allele [a 6-n-propylthiouracil (PROP) taster genotype] exhibit heightened sensitivity to bitter compounds, which may impact food choices and contribute to dietary avoidance of bitter but nutritionally beneficial foods [4, 36–38]. Such phenotypic taste differences can now be identified using validated clinical gustatory tests (e.g., taste strips, solutions), which could help screen individuals at risk of metabolic diseases, including obesity and diabetes [3, 4, 36]. Moreover, pharmacologic agents that modulate the taste receptor expression based on an individual’s genotype may offer a novel therapeutic avenue [37]. Nevertheless, further large-scale molecular and clinical studies are warranted to validate these associations and uncover the underlying mechanisms driving gene-diet interactions in T2DM.