Helicobacter pylori (H. pylori), a chronic infection of the gastrointestinal tract, has a higher prevalence in developing countries and is a global public health problem (Zamani et al., 2018). H. pylori can make functional dyspepsia, chronic gastritis, gastric ulcers, and even gastric cancer (McColl, 2010). In recent years, there are more and more studies on H. pylori and extra-gastric diseases, such as dermatological, cardiovascular, neurological, immune, respiratory, blood system, and metabolic diseases (Wong et al., 2014; Yu et al., 2019; Santos et al., 2020; Wang et al., 2020; Doheim et al., 2021; Reuter et al., 2023). H. pylori can turn out a variety of inflammatory factors, like C-reactive protein, interleukin, tumor necrosis factor α (TNF- α), and reduce the level of leptin (Noach et al., 1994; Perri et al., 1999; Chen et al., 2021). High levels of inflammatory factors and leptin deficiency are key mechanisms of insulin resistance (IR) and metabolic syndrome (Longo-Mbenza et al., 2007; Li et al., 2022).

Diabetes is a chronic metabolic disease with a rising global prevalence and a huge economic burden (Yazdanpanah et al., 2017). Glycated hemoglobin A1c (HbA1c) ≥6.5% has been included in the diagnostic criteria for diabetes mellitus, representing last 2 or 3 months of glycemic control (American Diabetes Association, 2009; Hinzmann et al., 2012). IR plays a crucial part in a variety of diseases, including diabetes and cardiovascular disease (Stumvoll et al., 2005; Wang et al., 2018; Adeva-Andany et al., 2019). Hyperinsulinemic-Euglycemic Clamp (HIEC) is that the gold criterion for designation of IR, however, owing to its complexity and high cost, it is difficult to be introduced in the physical examination population (Cersosimo et al., 2014). The triglyceride glucose (TyG) index is a novel clinical alternative index for IR (Guerrero-Romero et al., 2010; Lee et al., 2016). Because of its simplicity, accessibility and reproducibility, it has received much attention in risk and diagnostic studies for the development of type 2 diabetes (Lee et al., 2014; Wang et al., 2021).

However, the connection between H. pylori and HbA1c as well as IR is controversial. In a cross-sectional study involving 37,263 people, H. pylori infection was associated only with dyslipidemia, not fasting blood glucose (FBG) or HbA1c (Kim et al., 2016). In addition, H. pylori infection failed to take issue between diabetic and non-diabetic populations, and H. pylori eradication had no result on blood glucose and IR (Park et al., 2005; Demir et al., 2008). However, in some researches, H. pylori infection has been related to glycemic management in diabetic populations, and wipeout of H. pylori may benefit glycemic management (Cheng et al., 2019; Song et al., 2021).

Given the unspecified association between H. pylori and HbA1c, the research explored the influence of H. pylori infection on HbA1c and IR through a large cohort study.

Diabetes is a chronic metabolic disease whose progression can result in a series of complications such as retinopathy, cardiovascular-related problem, and neuropathy (Cole and Florez, 2020). Blood glucose control is essential in the management of diabetes to delay the emergence and progression of its complications (Vilsbøll et al., 2018; Wang and Hng, 2021). HbA1c, as a serological indicator of glycemic control, is important for preclinical diagnosis of diabetes and prevention of vascular complications (Heianza et al., 2012; Krhač and Lovrenčić, 2019; Halalau et al., 2023). HbA1c between 5.7-6.4% has been used by American Diabetes Association (ADA) as one of the diagnostic criteria for prediabetes (American Diabetes Association, 2021). Poor blood glucose control can lead to an increased prevalence of prediabetes, further increasing the risk of diabetes and its complications (Tabák et al., 2012).

H. pylori and diabetes are linked in many aspects, but studies on H. pylori and HbA1c are still relatively few, and there are different conclusions. In some meta-analyses, H. pylori was not detected to be related to glycemic control in diabetic population (Horikawa et al., 2014). However, in certain studies, H. pylori infection was positively correlated to HbA1c levels (Chen and Blaser, 2012). In our study, differences in HbA1c were identified in H. pylori negative and positive populations. Nonlinear relationship showed a striking increase in risk of H. pylori infection when the HbA1c >5.7%. This means that the population is more susceptible to H. pylori infection when there is a tendency towards early diabetes. Our further cohort study confirmed that long-term H. pylori infection resulted in apparently elevated HbA1c levels, but after eradication of H. pylori, HbA1c levels in the population decreased. It was consistent with some previous studies (Devrajani et al., 2010; Maluf et al., 2020). In addition, in our paper, the IR of the population was significantly higher with the increase of HbA1c. After prolonged H. pylori infection, IR levels were significantly higher than that of uninfected population, which may be closely related to the influence of H. pylori on glycemic control. However, the mechanisms by which H. pylori infection affects glycemic control and IR are complex. Type 1 diabetes mellitus (T1DM) is due to certain factors mediating autoimmune destruction of the pancreas, resulting in insufficient insulin secretion, while type 2 diabetes mellitus (T2DM) is mainly caused by impaired islet function and IR (Ilonen et al., 2019; Bonora et al., 2022). H. pylori may modulate the autoimmune response and IR syndrome through chronic inflammation outside the stomach (Polyzos et al., 2011; Marietti et al., 2013; Blosse et al., 2018). It can lead to the destruction of pancreatic islet cells and aggravate insulin secretion deficiency (Wang et al., 2022). In addition, its induced gastritis may affect the abnormal secretion of various hormones and further aggravate IR (Chen et al., 2021). Similarly, abnormal secretion of hormones such as ghrelin and leptin may cause changes in dietary intake, further affecting glycemic control (Aimasso et al., 2019).

Our cohort study, confirmed the nonlinear relationship between H. pylori and HbA1c, indicating that H. pylori can increase HbA1c levels and have an effect on IR. However, this research still has some limitations. First, it was a single-center study, which may require a multicenter longitudinal study to provide additional evidence. Second, mechanism by which H. pylori affects glycemic control is uncertain and perhaps needs to be further explored by biological experiments. Third, there was a lack of analysis of certain confounding factors, such as exercise and obesity, which may affect HbA1c levels (de Moura et al., 2023). In addition, although we did not use the homoeostasis model assessment of IR (HOMA-IR) to measure IR in the physically examined population because fasting insulin levels were not measured, the TyG index has been extensively studied as an alternative indicator of IR (Minh et al., 2021; Lopez-Jaramillo et al., 2023).

H. pylori is closely related to glycemic control in the population, and prediabetic populations may be more likely to be infected with H. pylori. Long-term H. pylori infection can increase HbA1c levels, worsen glycemic control, and exacerbate IR. Eradication of H. pylori has a positive impact on glycemic control in the population.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Ethics Committee of Taizhou Hospital (K20220790). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

JZ made great contributions to the concept, design and data acquisition of the article. YC and CY was mainly involved in data analysis. NY was involved in article writing. All authors contributed to the article and approved the submitted version.