Tuesday, May 19, 2015

Magnesium & Type II Diabetes - Link not as Straightforward as Some Experts & Supp. Recommendations Suggest

If Mg is the solution, then in form of high Mg foods, not supplements.
If you've ever googled "magnesium and diabetes", you will probably have read a sentence like this "magnesium (Mg) is actively involved in a number of metabolic reactions as an important co-factor with special emphasis on carbohydrate metabolism (Mooren. 2015). Unlike the latest paper by the German scientists Frank C. Mooren from the Justus-Liebig-University in Giessen from which I've grabbed the previously cited statement, your Google results will yet probably have treated this observation as if it was conclusive evidence that the provision of extra-magnesium would solve the T2DM-crisis of the Western wordl.

In his review, Mooren doesn't make the same mistake, instead he provides a brief, but in-depth overview of the regulation of intra- and extracellular Mg and the regulatory role of Mg in important metabolic pathways involved in energy metabolism and glycaemic control.
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An overview Mooren concludes by stating that a "critical consideration of the pros and cons of a Mg replacement therapy" that accounts for various "parameters such as Mg status, stage of disease and glycaemic control" is still lacking.

The fact that we do not yet understand all the confounding factors, though, does not mean that we are still completely in the dark. Rather than that we do know that,,,
  • ...diabetes predisposes to magnesium deficiency - It may seem to be a chicken or egg question, but an impartial review of the evidence suggests that diabetes or rather pre-diabetes comes first and hypomagnesaemia = low magnesium levels are a consequence of the development of diabetes.

    Next to the low magnesium content of the pro-diabetic junkfood Western diet (Pham. 2014), recent data indicate that hyperglycaemia and resulting osmotic diuresis overwhelm the kidneys’ reabsorption capacity for Mg leading to hypermagnesuria. In conjuction with various disturbances of metabolic and electrolyte variables, such as hypokalaemia and metabolic acidosis, which are common among diabetics, the elevated glucose levels trigger a redistribution of Mg within its compartments that will eventually lead to the depletion of intracellular Mg and an enhanced urinary Mg excretion (Pham. 2014).
  • ...hypomagnesaemia accelerates the transition from pre- to full-blown diabetes - The hyperglycemia-induced depletion of magnesium levels triggers a viscous cycle, because a balanced Mg status seems to be an important prerequisite for an adequate carbohydrate metabolism.
Overall, there is no doubt that there is a strong independent relationship between low serum magnesium levels and metabolic syndrome (Odds ratio (OR)=6.8, CI95% 4.2-10.9).
Are we talking serum of intracellular Mg levels? Both serum and intracellular Mg levels were reduced in patients with metabolic syndrome and were inversely correlated with BMI. Hypomagnesaemia (=low serum levels) as well as intracellular Mg depletion have been shown to be more prevalent (23.2 % and 36.1 %, respectively) in T2DM patients than in control group (3.3 % and 9.8 %, respectively | de Lourdes Lima. 2009). The reason that intra-cellular levels may still be a better predictors of future disturbances in glucose metabolism is the time-course of magnesium depletion which will begin in the cells and surface in form of low serum magnesium levels only when the intracellular stores are already critically low.
Six cross sectional studies have also reported associations between magnesium intake and risk of metabolic syndrome were reviewed in a recent meta-analysis by Diaba et al. (2014). More than 24,000 individuals of both sexes have been included.
Figure 1: Multivariable adjusted odds ratios (95% CI) of having prevalent metabolic syndrome in participants with the highest level of dietary magnesium intake compared with those with the lowest (Diba. 2014).
Despite the fact that the data shows a 31% reduced risk of metabolic syndrome (see Figure 1) and a 17% reduced risk per 100mg/day of magnesium in the diet in subjects in the highest vs. lowest Mg intake groups, and were compared (OR=0.69, CI95% 0.59-0.81), the evidence from studies investigating the effects of oral Mg supplementation as an adjunct therapy for type 2 diabetes is quite heterogeneous.
Table 1: Absolute changes in fasting plasma glucose after Mg supplementation in people with impaired glucose regulation | FPG – Fasting plasma glucose; * indicates the inclusion of hypomagnesaemic subjects only (Mooren. 2015).
Fourteen randomized controlled studies have been identified which investigated the effect of Mg supplementation on type 2 diabetes (Table 3). In total, 825 people with diabetes were enrolled, who had suffered from the disease for a mean duration of about 10.8+4.1 years. 10 studies reported values for glycosylated haemoglobin (HbA1c) at study onset. Their long term glucose control failed the recommended values for diabetic patients (target range HbA1c from 6.5-7.5 %) as indicated by a mean HbA1c of 9.3+2.1 %. 3 studies included patients with initial HbA1c levels lower than 7.5 %. Serum Mg concentrations at study onset have been reported in 12 studies. 5 out of 12 studies included diabetic people with hypomagnesaemia (Mg < 0.74mmol/l), while patients of another 5 studies showed serum Mg levels in the lower segment of the normal range (between 0.74 and 0.85 mmol/l).

Different Mg salts (Mg-pidolate; Mg-lactate-citrate; Mg-oxide; Mg-chloride; Mg-aspartate; Mg sulfate) were applied during a wide range of treatment periods which lasted from 4-16 weeks (mean treatment duration 9.6 weeks). After Mg supplementation, only 50 % of the studies reported significant improvements in serum Mg (7 out of 14 studies). Such a limited supplementation efficacy might partially result from different bioavailabilities of the various Mg salts (organic vs. inorganic) applied" (Mooren. 2015).
In a similar vein, most of the studies did not observe significant improvements in glucose control and the long-term glucose measure HbA1c in response to magnesium supplementation (only 23% and 18%, respectivels). The closely related triglyceride levels were not affected in any of the studies.
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So is Mg supplementation useless? As Mooren rightly points out, the "results are somewhat surprising in the light of the previously shown epidemiological data about the relationship between altered Mg status and diabetic disease" (Mooren. 2015). This does not mean, though, that it was pointless to give mg supplements a try. In fact, the short duration of the majority of the studies (6 weeks in 6 out of 14 of the studies) may simply not have been enough to fully replete the intra-cellular magnesium stores of the subjects.

What should not be forgotten, though, is the fact that the two studies on subjects with the lowest serum Mg and highest HbA1c levels yielded the most beneficial results. Specifically for those with exuberantly high and badly controlled blood glucose levels the provision of Mg supplements in form of magnesium citrate or magnesium gluconate of which my previous review of the literature showed that they are the most bioavailable forms is clearly indicated | Comment on Facebook!
References:
  • de Lourdes Lima, Maria, et al. "Serum and intracellular magnesium deficiency in patients with metabolic syndrome—evidences for its relation to insulin resistance." Diabetes research and clinical practice 83.2 (2009): 257-262.
  • Dibaba, D. T., et al. "Dietary magnesium intake and risk of metabolic syndrome: a meta‐analysis." Diabetic Medicine 31.11 (2014): 1301-1309.
  • Mooren, Frank C. "Magnesium and disturbances in carbohydrate metabolism." Diabetes, Obesity and Metabolism (2015): Accepted Article.
  • Pham, Phuong-Chi T., et al. "Hypomagnesemia: a clinical perspective." International journal of nephrology and renovascular disease 7 (2014): 219.