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Metformine: indirecte oorzaak neuropathie

Langdurig metformine gebruik kan indirect de oorzaak zijn van een verergerende neuropathie of van een neuropathie en neuropathische pijn. En wel een vitamine B12 deficientie polyneuropathie.

Of: Long-term use of metformin is associated with malabsorption of vitamin B(12) (cobalamin; Cbl) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves. [1]

In een recente studie (2009) bleek dat diabetes patienten die langdurig metformine gebruikten inderdaad lagere vitamine B12 gehaltes in het bloed hadden en een ernstiger neuropathie dan de patienten die geen metformine gebruikten… De aanbeveling was dan ook om regelmatig de vitamine B12 gehaltes te checken:

Metformin exposure may be an iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should be considered upon initiation of, as well as during, metformin therapy to detect potential secondary causes of worsening peripheral neuropathy. 

Metformine B12 deficientie en B12 suppletie 

Let op dat de normale vitamine B supplementen soms niet voldoende vitamine B12 bevatten om het gebrek dat door metformine ontstaat op te heffen, dat bleek in 2011:

Het ging om een onderzoek onder 1621 50 plussers, zonder en om 6867 met diabetes, zonder dat insuline gegeven werd.

 B(12) concentraties onder 148 pmol/L  werden als deficient gezien.

De resultaten:

Biochemical B(12) deficiency was present in 5.8% of those with diabetes using metformin compared with 2.4% of those not using metformin (P = 0.0026) and 3.3% of those without diabetes (P = 0.0002).

Among those with diabetes, metformin use was associated with biochemical B(12) deficiency (adjusted odds ratio 2.92; 95% CI 1.26-6.78).

Consumption of any supplement containing B(12) was not associated with a reduction in the prevalence of biochemical B(12) deficiency among those with diabetes, whereas consumption of any supplement containing B(12) was associated with a two-thirds reduction among those without diabetes.

De conclusie:

Metformin therapy is associated with a higher prevalence of biochemical B(12) deficiency.

The amount of B(12) recommended by the Institute of Medicine (IOM) (2.4 μg/day) and the amount available in general multivitamins (6 μg) may not be enough to correct this deficiency among those with diabetes. [2]

Januari 2010: prof.dr. Jan M. Keppel Hesselink 

Referentie

[1] Wile DJ, Toth C. | Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. | Diabetes Care. | 2010 Jan;33(1):156-61. Epub 2009 Oct 21.

[2] Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP Jr. | Association of Biochemical B12 Deficiency With Metformin Therapy and Vitamin B12 Supplements: The National Health and Nutrition Examination Survey, 1999-2006. | Diabetes Care. | 2011 Dec 16. [Epub ahead of print]