We utilized a genetic method to investigate the cause-and-effect link between type 2 diabetes and PHN. The MR findings support an association between type 2 diabetes and PHN (IVW: OR = 1.508,95%CI = 1.003–2.267), P = 0.04). Early detection and intervention should be performed for this high-risk group to improve the prognosis through timely diagnosis and development of therapeutic strategies.
As most patients with HZ combined with diabetes mellitus are associated with microcirculatory disorders and peripheral neuropathy [25], resulting in severe and extensive skin lesions, not only the recovery time is long and there is severe neuralgia, but also the lesion site is easy to be infected, which worsens the wound and further affects the quality of patient's survival, and even threatens their lives [26]. The main reasons analyzed include: higher blood glucose concentration in diabetic patients provides favorable conditions for viral growth, reproduction, and proliferation. Moreover, sustained high blood glucose can trigger the activation of polyol bypass in the body [27], and eventually VZV infection occurs. It has also been suggested that impaired diabetes mellitus microcirculation causes a stress response in neurons, triggering reactivation of VZV[28], which leads to an increased risk of HZ and PHN. Together with the fact that diabetes mellitus patients are often associated with reduced immune function [29, 30](due to metabolic disorders, the body's natural and acquired immunity is impaired in a variety of defense functions, including phagocytosis, cellular bactericidal effects, serum conditioners, and cellular immunity), this may also increase the risk of infection.
Although the pathogenesis of PHN is still uncertain, studies have been conducted in an attempt to elucidate how PHN is linked to type 2 diabetes. First, some microorganisms can adhere better to high glucose host environments and, therefore, are more likely to have a poor prognosis for PHN in diabetes mellitus patients. Secondly, due to vascular lesions that reduce the blood supply to the surrounding tissues and the lack of nutrient factors for the damaged nerves, thus making nerve regeneration slower than normal, the pain is longer and more severe than that of the average patient with HZ and is, therefore, prone to be followed by PHN[31]. Prolonged pain might result in the onset of chronic inflammation, which in turn again increases the risk of developing PHN [32].
It has been found that fasting blood glucose, glycosylated hemoglobin level, and the occurrence of VZV infection interact with each other [33], and glycemic control is an important factor affecting the recovery process of patients with type 2 diabetes combined with VZV infection, so glucose-lowering treatment is very important. Compared with non-pharmacological hypoglycemia, Glucose-lowering (insulin or dimethylbicarb) combined with conventional therapy of HZ can better shorten the length of hospitalization and reduce neuropathic pain symptoms [21]. Meanwhile, localized skin conditions should be closely monitored clinically to prevent secondary infections and complications [34, 35]. However, not all glucose-lowering drugs have the same positive effects, and one report [36] in an Asian diabetic population suggests that dipeptidyl peptidase (DPP)-4 inhibitors may be involved in the regulation of immune function through CD 26, which in turn increases the risk of HZ.In addition, type 2 diabetes combined with HZ has a complex pathomechanism, acute condition, rapid evolution, prominent sequela, difficult treatment, and great pain for patients; therefore, we recommend that type 2 diabetic patients be vaccinated with HZ vaccine at an earlier stage so as to minimize the risk of HZ and PHN in diabetes mellitus patients.Finally, it is worth noting that although diabetic painful neuropathy (PDN) is a common sensory peripheral neuropathy in diabetic patients [37].If patients present with abnormal local skin sensation and obvious pain, but do not have the typical features of PDN, clinicians should be alerted to HZ and closely observe and give antiviral treatment as early as possible to decrease the frequency of PHN and enhance the standard of living for those with diabetes.
Compared with traditional observational studies, MR studies have a lower chance of being impacted by factors that can confuse the results and the reverse causality bias. However, our study also has some limitations. 1st, we restricted our analysis to participants from European populations, which may limit the transfer of our findings to other racial and ethnic groups.2nd, because our data were derived from GWAS, detailed clinical information was lacking, and subgroup analyses of specific factors.3rd, hypotheses may be violated due to horizontal pleiotropy, in which genetic variation affecting the results through pathways different from the exposure studied may introduce biased estimates; however, we performed several sensitivity analyses, including MR-PRESSO, heterogeneity tests, and omission analyses, which consistently supported our results.