Diabetic peripheral neuropathy is as a major cause for disability due to foot ulceration, gait disturbance, fall-related injuries, and even amputation. The prevalence of diabetic peripheral neuropathy is a function of disease duration; of all patients with diabetes, about 60 to 70% will eventually develop peripheral neuropathy, even though not all will suffer pain .
The aim of this work was to study the possible relation between vitamin D deficiency and diabetic peripheral neuropathy in a sample of patients recruited from Beni-Suef governorate, north Upper Egypt.
The study was conducted on 25 type 2 diabetic patients with diabetic peripheral neuropathy and 25 healthy controls. Sixty-four percent of the patients were found to have vitamin D deficiency, 28% were found to have vitamin D insufficiency, and only 8% of them were found to have normal serum vitamin D level.
Our findings are in accordance to the findings of Bayani and colleagues  who found vitamin D deficiency in 64.2% of their patients and vitamin D insufficiency in 25% and just 10.3% had normal vitamin D level.
A higher prevalence was found in a Korean study done by Lee and colleagues , 89% of their type 2 diabetic patients suffered vitamin D deficiency and only 9 out of 300 persons (3%) had sufficient vitamin D concentration. They attributed high prevalence of vitamin D deficiency to the little duration of sunshine in Korea.
Also, compared to healthy controls from the same geographical area, matched in sex and age, patients with diabetic peripheral neuropathy have significantly lower serum vitamin D level.
Supporting our findings, many recent studies found that serum vitamin D level in patients with diabetic peripheral neuropathy is significantly lower than that in healthy controls [16,17,18].
On the other hand, Tahrani and colleagues  and Usluogullari and colleagues  found no difference in the prevalence of vitamin D deficiency between diabetic peripheral neuropathy patients and controls. The contradiction between such results and our findings can be explained by, first, using different methods for diagnosis of peripheral neuropathy (they only used monofilament and vibration) and, second, neurophysiological tests had not been done.
Our study revealed that females with diabetic peripheral neuropathy had significantly lowered 25(OH) level than males. Similarly Lebanese and Japanese studies found that female patients with type 2 diabetes mellitus have had lower 25-OHD levels than male patients [21, 22]. In contrast, in an Iranian study, there was no significant difference between both genders in the vitamin D levels .
Gender difference in vitamin D level can be claimed to the interaction between circulating sex hormones and vitamin D concentrations. It is postulated that the observed effects of vitamin D are related to testosterone, which circulates at lower levels in females . Also, pregnancy and lactation are potential causes for vitamin D deficiency . Moreover, in the Arab world, while Arab males follow a western dress style, women usually dress in long clothes that cover a greater surface of the skin. Additionally, females have less outdoor activities as a result of cultural and religious habits .
Older adults have more liability for vitamin D deficiency as a result of many interacting factors: decreased the number of vitamin D receptor, intestinal resistance to calcium absorption in response to circulating 1,25(OH)2D, decreased skin production of vitamin D, and the aging kidney produces lesser amounts of 1,25(OH)2D .
Our findings failed to detect a significant relation between age of patients and vitamin D. In concordance with our study, Suzuki and colleagues  found no significant correlation between the age of type 2 DM patients and 25(OH)D level. Al-Timimi and Ali  found no significant difference between the serum 25(OH)D level of patients below the age of 40 and those above the age of 40. In contrast, Leila and colleagues  and Kafshani and colleagues  found that serum vitamin D levels of type 2 diabetes patients were significantly correlated with their ages. In our study, there was a great variability in the disease duration and most of our patients had poor glycemic control, this may explain the insignificant relation between the age of patients and vitamin D level.
In this study, there was no significant relation between the level of HbA1c and serum vitamin D level. Similarly, Olt  and Usluogullari and colleagues  failed to detect a relationship between HbA1c and serum 25-OH vitamin D levels and stated that HbA1C levels were similar across groups with different 25-OH vitamin D concentrations.
Additionally, Al-Sofiani and colleagues  found that glycemic control did not differ between diabetic patients with vitamin D insufficiency or deficiency as compared to diabetic with normal vitamin D level. This means that the effect of vitamin D on diabetic neuropathy did not depend on the glycemic control.
In contrast, other studies demonstrated a negative correlation between HbA1C and serum vitamin D level [22, 32].
It has been postulated that vitamin D deficiency may enhance diabetic nerve damage and may impair nociceptor function. As a result, diabetic patients will experience pain at a threshold of serum 25-OHD higher than that in the nondiabetic population .
For statistical purposes, we have divided our patients according to the score of Michigan neuropathy screening instrument physical examination into two groups (above and below 4); our results showed that diabetic peripheral neuropathy patients who scored more than 4 had a significantly lower serum vitamin D level.
Similarly, Shehab and colleagues  found that Neuropathy Disability Score showed significant positive correlation with vitamin D. Also, Basit and colleagues  who studied 143 participants known to be type 2 diabetes with diabetic neuropathy and assessed neuropathic pain using Douleur Neuropathique 4 (DN4) score, total McGill pain score, and Short Form McGill Pain Questionnaire (SFMPQ) score. 40.5% patients showed evidence of vitamin D deficiency. A single intramuscular dose of 600,000 IU vitamin D resulted in a significant increase in vitamin D level and a reduction in positive symptoms on the DN4, total pain score, and SFMPQ.
In contrast, Chyachi and colleagues  found no significant association between the level of 25-hydroxyvitamin D and the severity of diabetic neuropathy. Different findings could be attributed to using different scores in the assessment of the severity of diabetic peripheral neuropathy.
A long duration of diabetes and poor glycemic control potentiate metabolic derangements, the production of glycosylation end products, oxidative stress, and endothelial injury . For statistical purposes, we have divided our patients according to duration of diabetes mellitus into two groups: diabetic peripheral neuropathy patients with disease duration less than 5 years and more than 5 years. There was no significant difference between both groups regarding serum vitamin D level.
Similarly, the study done by Al-Agha and Ahmad  in Saudi Arabia revealed insignificant difference between different serum vitamin D levels regarding disease duration (more and less than 5 years). In contrast, Al-Timimi and Ali  studied serum 25(OH) D in 337 Kurd patients with DM type 2 and found that serum 25(OH) D levels was statistically lower in patients with a diabetes duration more than 5 years compared to duration less than 5 years.
The discrepancy in the results could be explained by the different cutoff points used to classify patients as on sufficient vitamin D status, the difference in the sample size of the patients. Also, in our study, most of the time, there is uncertain delay between the occurrence of the disease and its discovery (low socioeconomic level and limited health resources).
Vitamin D deficiency has a negative effect on beta cell function, decreases insulin sensitivity, and increases insulin resistance .
In the present study, serum vitamin D level is not related to whether the patients are currently receiving insulin, oral hypoglycemic drugs, or combined therapy. Similarly, Kos and colleagues  in their study which includes 706 type 2 diabetic patients with a wide range of age (20 to 93 years) found no statistically significant difference between users and nonusers of metformin as an oral hypoglycemic agent regarding serum vitamin D level.
Many studies found that 25(OH) vitamin D levels of the insulin-taking patients were lower than that of the oral hypoglycemic drug-taking patients and control group. And that DM patients treated with insulin had the highest DPN prevalence [40,41,42].
These findings could be explained by the failure of diet and various oral hypoglycemic agents singly or in combination before starting insulin therapy. So, such patients could have several periods of poor glycemic control before the therapy was intensified .
In our study, NCS including median nerve (motor and sensory), ulnar nerve (motor and sensory), tibial nerve (motor), peroneal nerve (motor), and sural nerve (sensory) was done to all patients and revealed no significant relation to different serum vitamin D levels.
Similarly, in Shehab and colleagues’  study, motor nerves include peroneal, tibial, median, and ulnar nerves and the sensory nerves include sural, median, and ulnar nerves. None of the nerve conduction scores showed significant association with vitamin D status.
Additionally, another study included 112 type 2 diabetic patients with diabetic peripheral neuropathy divided to a treatment group with vitamin D and a placebo group. No difference was observed for Neuropathy Disability Score and nerve conduction study between the two groups after treatment .
The pathophysiology of the peripheral neuropathy in diabetes is complicated and other causes such as poor glycemic control and metabolic syndrome are involved. This can explain the absence of direct correlation between vitamin D level and the results of nerve conduction studies.