Previous research suggests that homeostasis of essential trace elements, especially zinc, can be disrupted by diabetes mellitus.5
Our data showed that zinc supplementation causes an increase in serum zinc level, as reported in other studies.14
Vitamins and minerals play diverse roles in the human body, not only in preventing deficiency diseases but also in regulating metabolism, gene expression, and influencing the development and progression of many chronic diseases. There is experimental and clinical evidence, especially in developed countries, supporting an alteration of zinc metabolism in patients with diabetes.1
However, only a few studies have examined the relationship between zinc and diabetes in developing countries.17
The mean serum zinc level in healthy individuals has varied from 11.4 μmol/L to 17.8 μmol/L.18
A study in Iran by Al-Maroof and Al-Sharbatti19
reported a lower mean serum zinc value (9.40 μmol/L) among diabetes patients. We observed a mean zinc level of 10.29 μmol/L (SD 7.50 μmol/L) in 96 diabetes patients who have been on treatment over a period ranging from 2 years to 22 years. This is lower than that (11.30 μmol/L) reported in a study of 110 Tunisian adult diabetics (both type 1 and type 2).5
When the cutoff level of <10.7 μmol/L was used to define zinc deficiency, 65% (n = 63) of patients had serum zinc levels below this cutoff level in our study. However, we did not consider serum measurements of different antioxidants in the supplementation, as their effectiveness has already been proven.4
We observed that group A had a mean change of −0.33 mmol/L in blood glucose level, whereas group C (placebo-controlled group) had a +0.43 mmolL change in blood glucose after 4 months of supplementation. Therefore, we can speculate that, overall, there is a 0.76 mmol/L (14 mg/100 mL) difference with zinc+MVM supplementation among diabetes patients. Further, we have shown that zinc supplementation (with or without other MVM) was effective in reducing FBS in partially controlled adult diabetics (FBS > 100 mg/dL) who were on long-term follow-up. Furthermore, supplementation significantly improved PPBS and HbA1C
% levels when compared with placebo. This was similar to the results reported by Hussain et al20
that showed a 25% reduction in FBS and a 17% reduction in HbA1C
% with 3 months’ supplementation with zinc and melatonin. In our analysis, the mean HbA1C
% of the supplemented groups (zinc+MVM and MVM groups) reduced significantly by 0.3 ± 0.8% at the end of 4 months of follow up, whereas no significant change was found in the control group. The significant changes observed in the supplemented groups refer to the effective improvement in their glycemic control in response to zinc and other multivitamin and mineral supplementation. Our observations are consistent with the results of other trials that examined the effect of zinc supplementation on patients with type 2 diabetes.5
The significant negative correlation we observed between the change in serum zinc level after supplementation and the baseline serum zinc level suggests that zinc-deficient individuals had greater absorption of zinc than individuals with higher zinc levels at the baseline. This finding is consistent with the results of other studies, suggesting that zinc treatment will have a high chance of success in changing zinc status in zinc-deficient subjects.21
In addition, we observed that baseline serum insulin levels were positively correlated with final serum insulin levels and negatively with mean change after the intervention (data not shown). Previous studies examining the effect of zinc supplementation on insulin level are sparse. Hussain et al20
found no change in serum C-peptide level with zinc supplementation. However, we require studies with longer follow-up to see whether an increase in insulin secretion is sustained over a longer time period. Zinc treatment has also been shown to raise body defenses in immune-suppressed patients.22
It is important to note that a large proportion of subjects in our study had a low serum zinc level at the baseline and that daily administration of zinc for 4 months resulted in almost double the baseline value (mean improvement + 12.44 μmol/L). We have not addressed issues related to immune status in the current study, and the clinical importance of the high prevalence of zinc deficiency among adult diabetics is not known to us.
Treatment with MVM with or without zinc reduced TC, TG, and LDL plasma levels and increased HDL levels. These observations are consistent with those reported by Kadhim et al,23
whereby a group of poorly controlled diabetes patients were supplemented with zinc and melatonin for a period of 3 months. In the current study, we observed a significant decrease in TG concentration (mean change of −0.07 mmol/L; P
< 0.05) only in the MVM group. Partida-Hernández et al,24
however, showed a significant decrease in TG concentration following 12-week supplementation with 100 mg zinc sulfate among diabetics who were not on cholesterol-lowering treatment. Furthermore, they showed a significant reduction in TC and an increase in HDL cholesterol, indicating that supplementation, in addition to improving glycemic indices, has favorable effects on other cardiovascular risk factors. Even though we have shown a similar trend, the reduction in TC and the effect on HDL levels were not as great as they reported. Most of our patients were already on cholesterol-lowering drugs and, as such, they may have achieved the “desired” lipid targets at the study entry.
Garber and Karlsson25
showed that the treatment of dyslipidemia in diabetes must be focused on several targets involving glycemic control and reduction of LDL levels. The results of the present study are agreeable with these suggestions. There is evidence suggesting that zinc can act as an endogenous protective factor against atherosclerosis by inhibiting the oxidation of LDL in the presence of transition metals,26
and that adequate zinc nutrition may protect against inflammatory diseases such as atherosclerosis by inhibiting the activation of oxidative stress responsive transcription factors as well as the expression of inflammatory cytokines.
The present intervention did not show any significant effect on renal functions measured by serum as well as urine creatinine, and our observations are similar to those of Khadim et al.23
In contrast, a significant improvement in renal function has been observed in a previous study27
after 60 days of supplementation. One limitation of our study is that we did not measure urinary microalbumin levels of the patients.
We performed this study in a single-blinded manner for logistical reasons, and this may have reduced the validity of data. This is one of the limitations in the study, as expectation bias or change in the behavior of the study subjects may have affected the results. However, only the FBS results were given to the clinicians at the follow-up sessions of their respective clinics. Secondly, we did not measure the change in physical activity and anthropometry because of the short duration (4 months) of follow-up. Therefore, we were unable to comment on the effect on anthropometry (ie, body mass index) with the intervention. Further, the small sample size may have contributed to inconclusive results seen in some analyses. To minimize the effects of disparity in baseline values between groups (ie, high HbA1C% levels in the zinc+MVM group over the other two groups), we included baseline measurements in each analysis as a cofactor (see Statistical analysis). Although physicians were free to make changes in the management of these patients, no changes in the major drugs such as antidiabetics, antihypertensives, or lipid-lowering therapy were made during the trial period. Apart from the trial drug, we inquired about the patients’ compliance to their regular medication as well. However, there is still a possibility that patients may have changed their behavior (ie, diet and physical activity) during the trial period, but we expected it to be uniform in all three groups. This altered behavior can considerably limit the study outcome.
Data on dietary intake or serum zinc levels are limited to young children and adolescents8
in Sri Lanka. Baines and Roberts29
have reported that if the intake of zinc is marginal, it can have a major impact on food intake by reducing taste sensation. As taste is already impaired in the elderly, this can seriously affect food choice. Zinc is readily available in animal foods, especially red meat, liver, fish, and eggs. If this is not feasible, then the use of a multivitamin and minerals supplement may be a suitable alternative. However, multiple medication use is prevalent in this population, and another pill may add to the confusion.
In conclusion, the supplementation of zinc with other multimineral vitamins daily for a period of 4 months to adult diabetes patients on standard diabetic care demonstrated favorable changes in metabolic profile, including better glycemic control and desirable changes in lipid profile. Based on the results presented in this report, it can be concluded that zinc, either alone or in combination with other known antioxidant minerals and vitamins, may have supplementary benefits in the routine management of adult diabetes.