Expression of Concern (20 ^th October 2023): We, the Publisher and Editor of F1000Research, are issuing an Expression of Concern for the following article:

Faris Raheem M, H. Ali S and G. Shareef L. Impact of serum levels of vitamin D on lipid profiles, glycemic indices, and insulin resistance in obese type 2 diabetes patients: An observational study [version 1; peer review: awaiting peer review]. F1000Research 2022, 11:1002 ( https://doi.org/10.12688/f1000research.125191.1).

After publication of this article, questions about the integrity of the ethical approval and methodology were brought to the attention of the F1000 Editorial Team. We have reached out to the authors requesting that they respond to the concerns raised and provide additional information to support the integrity of the content. However, despite multiple attempts to contact the authors, and their institution, they have not responded to our queries within the requested timeframe. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. The authors have been sent notification about this Expression of Concern.

Editorial Note (13 ^th July 2023): Since publication, concerns have been raised to the Editorial Team regarding the ethical approval for this study, as well as overlap in the sample and methods to other papers by these authors. The Editorial Team requested explanations regarding the similarities on 19 ^th May and 6 ^th June 2023, and the institution was contacted on 21 ^st March, 6 ^th April and 25 ^th April 2023 to verify the ethical approval. Neither the author nor institution have provided responses to our requests. The Editorial Team will update this Editorial Note as the situation progresses. Peer review activity has been suspended for this article until we receive an explanation from the authors/institution.

Diabetes mellitus (DM) is a metabolic disorder specified by persistent hyperglycemia with varying degrees of deterioration in the metabolism of carbohydrates, lipids, and proteins. ^{1 , 2} Thus, diabetes patients have a higher chance of developing dyslipidemia ³ and increased release of free fatty acids, which participate in developing insulin-resistant fat cells. Meanwhile, high concentrations of free fatty acids stimulate the creation of triglycerides; this boosts the release of apolipoprotein B (ApoB) and very low-density lipoprotein (VLDL), both have been related to an elevated risk of cardiovascular disease (CVD). ⁴ Furthermore, hyperglycemia also has a negative effect on lipoproteins (especially low-density lipoprotein (LDL) and VLDL) by elevating their glycation and oxidation, thereby promoting the progression of aggressive atherosclerosis. ⁵

On the other hand, vitamin D insufficiency is linked to the evolution of T2DM. ⁶ Therefore, mild vitamin D deficiency is linked to insulin resistance in several pathways, including low-grade inflammation caused by an unbalanced innate immune system, associated pro-inflammatory cytokines, and enhanced acute phase reactants. ⁷

This research aims to investigate the effects of vitamin D serum level on glycemic indices in relation to lipid profile in Iraqi obese type 2 diabetics compared to healthy controls with comparable vitamin D levels.

The diabetics' groups had higher FSG, Insulin, HOMA-IR, and HbA1c levels compared to the control groups. However, for HOMA-IR, insulin, and HbA1c, there was no significant difference between the two diabetic groups or between the two control groups, The FSG patients with vitamin D level <22.5 ng/dl showed higher FSG level than patients with vitamin D level ≥22.5 ng/dl, as demonstrated in Table 2 and Figure 1. ¹⁷

There were no marked differences in TC, and LDL-C levels between the two control groups and the DM group with vitamin D level ≥22.5 ng/dl, while the DM group with vitamin D level <22.5 ng/dl showed significantly higher TC and LDL-C levels than the other three groups. There was no marked difference in TG level between the two DM groups or between the two control groups. DM patients with vitamin D level ≥22.5 ng/dl showed no difference with DM patients with vitamin D level <22.5 ng/dl group or with the two control groups, while the DM group with vitamin D level <22.5 ng/dl showed a significantly higher TG level than the two control groups. No marked difference in HDL-C serum level between the two diabetic groups or between the two control groups was shown. However, both control groups had a higher significant HDL-C value than the patient groups. The diabetic group with vitamin D levels <22.5 ng/dl showed higher TC: HDL-C ratio and TG: HDL-C ratio levels than the diabetic group with vitamin D levels ≥ 22.5 ng/dl and the two control groups, while DM patients with vitamin D level ≥22.5 ng/dl showed significantly higher values than the control group with vitamin D level ≥22.5 ng/dl and showed an insignificant difference with the control group with vitamin D level <22.5 ng/dl. No marked difference in serum level of LDL-C: HDL-C ratiobetween the two diabetic groups nor between the two control groups was shown. The DM group with vitamin D level >22.5 ng/dl showed a non-significant difference in LDL-C: HDL-C ratio level with the control group with vitamin D level <22.5 ng/dl, while the DM group with vitamin D level <22.5 ng/dl showed a significantly higher LDL-C: HDL-C ratio level than the two control groups as shown in Table 3. ¹⁷

For the current study, there were no marked differences in confounder (age, gender, BMI, and smoking) among the four studied groups. The diabetics' groups had higher FSG, fasting insulin, HOMA- IR, and HbA1c levels compared to the control groups due to the effect of diabetes. The findings in this study showed that vitamin D levels had no impact on the level of fasting insulin, HOMA-IR, and HbA1c as demonstrated in Table 2, and this finding highly agreed with Al- Shoumer et al. and Luo et al. who suggested in their research that there was no link between glycemic control and vitamin D when confounders like age, gender, and BMI were controlled. ^{18 , 19} This also agreed with research carried out by Olt S. et al. who suggested that vitamin D level wasn't correlated with glycemic control (For HbA1C correlation with vitamin D level, p = 0.33 (>0.05)). ²⁰ While Al-Timimi et al. reported that deficiency in vitamin D levels in patients with T2DM was significantly associated with glycemic control. ²¹ The correlation between vitamin D and HbA1c is controversial; many previously published studies have shown a significantly weak negative correlation between HbA1c and vitamin D levels. ^{22 , 23} Pittas et al. , in a retrospective study, suggested that impaired B-cell activity and insulin resistance are among the pathophysiological factors associated with metabolic syndrome and type 2 diabetes (T2DM). Vitamin D levels may indirectly impact these factors by regulating calcium homeostasis or activating vitamin D receptors. ²⁴ In this study, patients with vitamin D levels <22.5 ng/dl showed higher FSG levels than patients with vitamin D level ≥22.5ng/dl, which agreed with a study done by Scragg et al. who found an inverse relationship between vitamin D and FSG levels in their research. ²⁵ While a Japanese study comparing DM type, two patients and healthy controls found that vitamin D insufficiency was present in 70% of cases without a difference in vitamin D levels between patients and controls. ²⁶ Two US studies suggest an increase in the mean vitamin D level in T2DM and the corresponding controls. ²⁷ The variation in outcome among studies indicates that vitamin D levels in patients with T2DM differ according to ethnicity or other unknown causes. ²⁸ In the present study, levels of vitamin D showed a pronounced impact on TC, LDL-C, and TC: HDL-C ratio levels, but it didn’t show an effect on TG, HDL-C, TG: HDL-C ratio, and LDL-C: HDL-C ratio levels. DM in this study showed an impact on all lipid profiles. This finding agreed with many studies that reported dyslipidemia as an independent predictor of a decrease in vitamin D level. TC was reported to correlate inversely with serum levels of vitamin D even after controlling for confounders. ²⁹

This study's results disagree with many cross-sectional studies, where serum vitamin D levels correlate directly with HDL-C. Many investigations also revealed an oppositional relationship between TG and blood vitamin D levels. Although some research found a link between TG and blood vitamin D levels, other investigations found an opposite correlation. ³⁰ The current study findings are comparable to the research of John et al. on 170 Bangladeshi individuals born in the UK (101 female and 69 male) without a history of diabetes or other chronic illness. They found no link between vitamin D and HDL-C or TG levels. ³¹ Due to enhancing intestinal calcium absorption, research considering lipid metabolism has found that vitamin D can decrease hepatic triglyceride production and boost uptake by peripheral tissues. ³² Vitamin D boosts reverse cholesterol transport by increasing apo-lipoprotein A1, vitamin D also encourages the development of big HDL-C particles. ³³ Due to the interdependence of the metabolism of carbohydrates and lipids, blood lipid levels can be influenced by various variables in people with diabetes. As a result, every issue in lipid metabolism causes a disorder in glucose metabolism and vice versa. The primary defect in most people with type two DM is insulin resistance. Insulin resistance and hyperinsulinemia have a good predictive value for the development of T2DM in non-diabetic people. ³⁴ The TG: HDL ratio and other lipid profile ratios have been evaluated daily for many critical clinical uses. ^{35 , 36} Prior studies have suggested a positive correlation between metabolic syndrome, negative cardio-metabolic risk factor profiles, and the prediction of diabetes or its consequences. This can happen because of the link between insulin resistance and TG: HDL-C ratio. ³⁵

Elevated FSG, HOMA-IR, HbA1c, fasting insulin, triglycerides, TC: HDL-C ratio, TG: HDL-C ratio, and LDL-C: HDL-C ratio values were found in diabetes patients compared to healthy controls, with markedly diminished HDL-C levels in diabetes patients compared to healthy controls as a result of the diabetes effect. Vitamin D level significantly impacted total cholesterol, LDL-C, and TC: HDL-C ratio in obese diabetic patients.

Written informed consent for publication of the participants’ details was obtained from the participants.