Updates to LCA Framework

The proportion of females in this study was higher than the male counterpart in contrast to some previous documented reports of an overall higher prevalence of diabetes in males than females.

A possible explanation for this might be due to the higher life expectancy in females.⁹⁸ In part, this finding may be a reflection of the female to male sex distribution of the diabetes subjects attending the diabetes clinic of the Lagos University Teaching Hospital where this study was carried out; which was put at 1.8. Greater use of hospital facility by women or lack of time to visit hospital by employed males may also be a reason.

The mean HbA1c found in this study was lower compared to previous report of a mean HbA1c of 10.5% among T2DM subjects in this centre. The reason for this could be due to an

improvement in patients care. The proportion of subjects with poor glycaemic control seen in this study is similar to reports in other centres across the country, which ranged from 46% to 64%.^18-21

5.4.1. Prevalence of Vitamin D Deficiency in Persons with T2DM

The findings from this study, to a large extent corroborated with previous work in this field. The prevalence of vitamin D deficiency in this study is 63.2% and 53.3% in T2DM and controls respectively. This alludes to the widespread vitamin D deficiency and insufficiency in both apparently healthy populations and patients with various pathologies including diabetes mellitus.⁸⁵ The reported prevalence of vitamin D deficiency among persons with Type 2 diabetes mellitus ranges from 63.5% to 91.1%.^6,7

The finding of a lower serum calcium concentration in persons with T2DM compared to healthy control is consistent with those of other studies and may be due to the reported elevated urinary

excretion of calcium in T2DM.¹¹³ The finding of a predominantly normal calcium levels among the study participants vis-a-vis the extent of vitamin D deficiency status is as reported by

Sedrani.¹¹⁵ who found vitamin D deficiency in about 50% of the study participants and all had a normal serum calcium level.¹¹⁵

5.4.2. Association between Serum Vitamin D and Glycaemic Control

This study confirms that vitamin D3 level is inversely associated with HbA1C in persons with T2DM . This finding is similar to the NHANES report of a lower vitamin D levels and higher HbA1C levels in black subjects compared to their White counterparts.¹² Jung Re Yu, et al. also reported that high levels of HbA1C were independently associated with Vitamin D deficiency in T2DM patients.¹⁰⁷

5.4.3. Vitamin D3 Supplementation and Serum Vitamin D levels

Vitamin D3 supplementation in the treatment arm resulted in a significant increase in the serum vitamin D3 concentration after 12 weeks of treatment compared to the placebo group, although the serum vitamin D was still below normal. This may be due to the short duration of supplementation. Assessing the adequacy of vitamin D replacement can prove difficult. This is partly due to methodology issues for measuring vitamin D.⁶⁰ There is often a time lag in response of measured vitamin D levels to oral vitamin D replacement. This is due to the highly fat soluble nature of vitamin D and its distribution within the large body fat compartment, before distribution within the smaller extracellular fluid compartment. It takes several months to correct vitamin D deficiency.⁶⁰For monitoring of response to vitamin D replacement, it is best to measure serum vitamin D, 3 to 4 months after commencing therapy⁶⁰

5.4.4. Vitamin D3 Supplementation and Glycaemia

This study found a significant reduction in mean FPG from baseline values, a drop in HbA1c levels in T2DM subjects after vitamin D supplementation; while the FPG and HbA1c increased further in the placebo arm. Also, the proportion of T2DM subjects with poor glycaemic control who converted to good control after vitamin D3 supplementation was significantly higher in the Treatment group compared to placebo group.

These findings are in agreement with the results of previous studies.38, 64, 108-110 Amal, reported a significant reduction of the mean fasting blood glucose and HbA1C from baseline after six months of vitamin D3 supplementation.¹⁰⁹ Pittas et al.³⁸ in a double-blind, randomized, controlled trial reported that in healthy adults with impaired fasting blood glucose, supplementation with calcium and vitamin D may attenuate increases in glycaemia and insulin resistance that occur over time. In addition, a retrospective study conducted by Sabherwal et al.⁶⁴ indicated that, vitamin D and calcium replacement therapy in South Asian patients with T2DM produced a significant decrease in both HbA1c and weight, which might be attributed to the increase in vitamin D levels post-treatment. Consistent with finding of this study, Nikooyeh et al.¹¹⁰ showed that daily intake of a vitamin D-fortified yogurt drink, either with or without added calcium, improved glycaemic status in T2DM patients.

5.4.5. Influence of Vitamin D3 Supplementation on Insulin Resistance and Beta-cell Function

The finding of an improvement in insulin resistance after vitamin D3 supplementation in this study is consistent with findings from previous studies.^{111, 112} A randomized, placebo-controlled

trial concluded that improving vitamin D status in insulin resistant (IR) women resulted in improved IR and sensitivity, but no change in insulin secretion.¹¹²

There was no significant effect of vitamin D3 supplementation on pancreatic beta cell function (HOMA-B) in persons with T2DM compared to control. This finding is similar to that reported by Von Hurst, et al.¹¹²