Vitamin C in Diabetes and Kidney Dysfunction
Vitamin C Status in People with Types 1 and 2 Diabetes Mellitus and Varying Degrees of Renal Dysfunction:
Relationship to Body Weight
Diabetes mellitus is a complex disorder characterized by chronic metabolic dysregulation and potentially life-threatening complications. Type 1 diabetes mellitus (T1DM) results from a deficiency of insulin secretion and has genetic and autoimmune risk factors. The more common type 2 diabetes mellitus (T2DM) results from resistance to insulin action and may be present for many years before detection. Chronic hyperglycemia can result in severe complications such as nephropathy, retinopathy, neuropathy, and cardiovascular diseases. In 2019, worldwide cases of diabetes comprised approximately 463 million people, with approximately 38 million new cases of diabetes since 2017. Significant socioeconomic and ethnic disparities are observed in many regions of the world, including in Australia and New Zealand, where indigenous Aboriginal, Māori, and Pasifika peoples have a higher prevalence of T2DM and its associated complications.
Obesity is a major risk factor for diabetes, and research has indicated that the chronic low-grade inflammation and oxidative stress commonly observed in people with obesity and diabetes play a pivotal role in the development and progression of the disease. Oxidative stress is characterized by an imbalance in the generation of reactive oxygen species in the body and the ability of endogenous antioxidant systems to neutralize these. Vitamin C is an essential micronutrient with potent antioxidant properties. Epidemiological evidence indicates that higher plasma vitamin C concentrations are associated with decreased risk of developing T2DM. Vitamin C is able to scavenge a wide range of reactive oxygen species, thereby protecting essential biomolecules from oxidative damage. We and others have previously shown lower vitamin C status and a higher prevalence of hypovitaminosis C and outright deficiency in people with T2DM, despite comparable dietary intakes of the vitamin to healthy controls.
Of note, obesity was an independent predictor of vitamin C status in these cohorts. This finding suggests that the elevated inflammation and oxidative stress observed in people with diabetes and obesity may be depleting their vitamin C concentrations independent of dietary intake. Intestinal inflammation may also attenuate uptake of dietary vitamin C via the intestinal vitamin C transporter (SVCT1). Furthermore, there may be a volumetric dilution effect in people with higher body weight. This premise is supported by a supplementation study indicating lower plasma vitamin C concentrations in people with higher body weight, despite comparable vitamin C intakes. Other research has suggested that lower vitamin C status in patients with both T1DM and T2DM may be due to enhanced renal excretion in those with evidence of underlying renal disease.
A number of studies assessing vitamin C status in people with diabetes have included both T1DM and T2DM; however, fewer studies have directly compared the vitamin C status of people with T2DM relative to those with T1DM. Some have found lower vitamin C status in people with T2DM relative to those with T1DM, whilst others have found comparable vitamin C status between the two types. The primary aim of the current study was to explore the associations between plasma vitamin C and markers of renal and cardiometabolic health, with a focus on obesity, in people with diabetes. A secondary aim was to provide a descriptive comparison of these markers by diabetes diagnosis (T1DM or T2DM), noting that there are inherent cardiometabolic differences between these two types of diabetes.
In our cohort of patients with T1DM and T2DM, who had been selected to have a comparable proportion of renal dysfunction, we found low vitamin C status and a high prevalence of hypovitaminosis C in those with T2DM relative to T1DM. Bodyweight was a significant predictor for low vitamin C status and accounted for one-third of the difference in vitamin C status between those with T2DM and T1DM. This finding could be due to a volumetric dilution effect and/or enhanced utilization of the vitamin due to obesity-related inflammation and oxidative stress. Our finding suggests that obese people with diabetes may have higher requirements for vitamin C, and supplementation may be required to restore adequate vitamin C status. The doses required remain to be established.
Diabetes mellitus is a chronic metabolic disorder and is associated with depleted vitamin C status.
The underlying aetiologies and pathogeneses responsible for this association are poorly understood. This retrospective study explored the vitamin C status of 136 adult outpatients with types 1 and 2 diabetes mellitus (T1DM/T2DM), with a focus on indices of renal function and metabolic health, including body weight.
In the T1DM group (n = 73), the median plasma vitamin C concentration was 33 (18, 48) µmol/L, with 37% hypovitaminosis C and 12% deficiency. In the T2DM group (n = 63), the median plasma concentration was 15 (7, 29) µmol/L, with 68% hypovitaminosis C and 38% deficiency.
Lower vitamin C was associated with macroalbuminuria (p = 0.03), renal dysfunction (p = 0.08), and hypertension (p = 0.0005). Inverse associations were also observed between plasma vitamin C and various other metabolic health parameters (p < 0.05), especially body weight (p < 0.0001), which was higher in those with hypovitaminosis C (<23 µmol/L; p = 0.0001).
The association with bodyweight remained, even after multivariable analysis. In summary, body weight was a significant predictor of low vitamin C status in people with diabetes. This suggests that people with both diabetes and high body weight may have greater than average vitamin C requirements.
Vitamin C Status in People with Types 1 and 2 Diabetes Mellitus and Varying Degrees of Renal Dysfunction: Relationship to Body Weight
by Anitra C. Carr, *ORCID, Emma Spencer 1ORCID, Helen Heenan, Helen Lunt, Monica Vollebregt, and Timothy C. R. Prickett
Antioxidants 2022, 11(2), 245; https://doi.org/10.3390/antiox11020245