Prediabetes, Lipid Regulation and Vitamin D

Tempo de Leitura: 4 minutos

In recent years the prevalence of diabetes mellitus has increased significantly worldwide. Research estimates that in 2011, there were approximately 366 million patients with diabetes and that the number is expected to reach 552 million by 2030. From another perspective, vitamin D deficiency is also a growing health problem in many parts of the world, affecting more than 50% of the general population. Therefore, data from the literature show a possible association between vitamin D levels in the regulation of lipid levels in prediabetic individuals.

Prediabetes precedes diabetes, a disease that is associated with a high risk of cardiovascular disease, mortality and high economic costs related to treatment, and associated work disability. With this, a intervention during prediabetic status is important for preventing the progression of diabetes. Prediabetes is defined as a state with a blood glucose level beyond the normal value, but which does not meet the diagnostic criteria for diabetes, which include: altered fasting glucose, defined as fasting plasma glucose of 6.1–6.9 mmol/L or 5.6–6.9 mmol/L; decreased glucose tolerance, defined by the oral glucose tolerance test with plasma glucose value in the range of 7.8–11.0 mmol/L; or glycated hemoglobin levels between 39 and 47 mmol/mol.

It is worth noting that dyslipidemia is an important feature of both prediabetes and diabetes and can aggravate diabetic complications.. Given this, the literature shows that people with lower levels of 25-hydroxy vitamin D (25(OH)D) tend to have higher blood glucose levels, insulin resistance, and a higher risk of type 2 diabetes mellitus (T2DM), just as vitamin D supplementation has been shown to improve dyslipidemia in individuals with T2D.

Vitamin D and Lipid Markers

Many studies have shown that low serum 25(OH)D concentration was associated with adverse lipid state. With this some research has indicated that vitamin D supplementation could improve serum levels of total cholesterol, low-density lipoproteins, high-density lipoproteins and triglycerides in patients with T2DM, as well as in individuals with metabolic syndrome.

In contrast, the meta-analysis discussed here presented results that vitamin D supplementation may decrease circulating triglyceride levels in individuals with prediabetes, especially in certain situations, but failed to confirm the effects on serum levels of total cholesterol, low-density lipoproteins, high-density lipoproteins.

Physiological Action of Vitamin D and Triglyceride Levels

The effects on the body of vitamin D supplementation on triglyceride levels can be mediated by several factors, as the following are:

  1. Increased calcium levels;
  2. Suppression of parathyroid hormone secretion (PTH);
  3. Inhibition of lipolysis;
  4. Suppression of inflammation;
  5. Suppression of the activity of the renin-angiotensin-aldosterone system;
  6. Interaction with glucocorticoids and sex hormones;
  7. Adiponectin upregulation;
  8. Improvement in insulin resistance and insulin levels;
  9. Direct inhibition of the expression of the binding protein of the nuclear factor 1c sterol regulatory element (SREBP1c) involved in hepatic triglyceride synthesis;
  10. Increased TG clearance by upregulation of lipoprotein lipase, neutral sphingomyelinases, PPARγ and adipocyte-binding protein 2;
  11. Positive regulation of mitochondrial oxidation.

Interpreting Literature

As previously mentioned, vitamin D supplementation especially in certain situations showed more positive results, one of them was in the intervention group that included obese individuals. In other words, studies that included obese individuals with prediabetes, not just normal-weight and overweight individuals, observed a more significant effect on triglyceride levels when compared to studies that did not include obese individuals.

These points can be explained by the fact that in some of the studies were included in addition to obese individuals, male individuals. Thus, in the subgroup analysis the effect of supplementation in triglycerides was more marked in mixed sex studies than in studies that included only women, in which the effect was not significant. In addition, the intervention time of the studies may also influence the results obtained. Better speaking, studies that included obese subjects treatment was longer than one year, while the duration of treatment in the study that excluded obese subjects was 8 weeks.

On the other hand, in a more direct association, the reduction of triglycerides in obese individuals may have been more significant for the fact that these have much higher triglyceride levels compared to non-obese individuals. Therefore, the effect may be more observable, especially during prolonged treatment. Furthermore, another explanation may be due to the fact that obese individuals are more prone to vitamin D deficiency, while improvements in insulin resistance and related metabolic characteristics can be observed after its correction. Despite the hypotheses raised, these were not confirmed in the studies.

Regarding vitamin D supplementation doses, the results show that the relatively low dose (2,857 IU/day) and relatively high dose (8,571 IU/day) provided significantly greater reductions in triglycerides., but no such effect was observed in the relatively average group. However, the relatively average dose group included only one study and it was short-lived.

Briefly, interventions that last only a few months may be a very short period of time to evaluate the benefits of vitamin D. Therefore, interventions involving supplementation for a period of less than 1 year are not sufficient to observe the effects of supplementation. In this sense, the greatest reductions were observed in patients with long-term interventions, but not in the short-term subgroup.

Clinical practice

The data presented show that vitamin D supplementation can beneficially affect triglyceride levels in individuals with prediabetes. Treatment with long durations and doses that correct vitamin deficiency/insufficiency may have a beneficial effect on the lipid profile. In addition, the literature highlights the importance of a regular assessment of vitamin D status among patients with prediabetes.

Bibliographic references

Suggested reading:
Vitamin D

Watch the video on Science Play with Fábio dos Santos: Vitamin D: far beyond a vitamin

Vitamin D and lipid levels
s: Yang Y, Yan S, Yao N, et al. Effects of vitamin D supplementation on the regulation of blood lipid levels in prediabetic subjects: A meta-analysis. Frontiers in Nutrition. 2023;10. doi:

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