A Low Magnesium Diet Worsens Metabolic Disturbances And Insulin Sensitivity In Diabetic Mice
Authors: Smith Alexander J. , Challburg Jessica , O'Farrell Andrew L. , Duke Brian , Symons J. David , Jalili Thunder 
Published: November 2023

Nearly 60% of United States adults do not consume the recommended intake of dietary Magnesium (Mg). Mg participates in more than 300 enzymatic reactions and stabilizes ATP during phosphorylation / dephosphorylation events. Epidemiological data associates low Mg intake with greater risk of Metabolic Syndrome / diabetes, and Mg status is often compromised in diabetic patients. It remains unclear whether low Mg consumption exacerbates, or Mg supplementation alleviates the metabolic disruptions that occur during diabetes.We hypothesized low dietary Mg during the development of diabetes would alter metabolic rate, and worsen glucose tolerance / insulin sensitivity. This hypothesis was tested using TallyHo (TH) mice that develop Type 2 Diabetes by 16 weeks of age. Three cohorts (n=8 each) of 8 week‐old TH mice were fed special diets for 8‐weeks. Group 1: TH + Low Mg diet (L‐Mg, 100mg Mg Oxide / kg chow). Group 2: TH + Standard Mg diet (S‐Mg, 500mg Mg Oxide/ kg chow). Group 3: TH + High Mg diet (H‐Mg, 1000mg Mg Bisglycinate / kg chow). Age matched male C57BLK6J mice fed standard diets served as controls (Con, n=8, 500mg Mg Oxide/ kg chow).Energy expenditure (Cal/hr/g body weight) and oxygen consumption (mL/h) were similar in S‐Mg and H‐Mg vs. Con, but lower (p<0.05) in L‐Mg Low Mg vs. Con. All groups had greater (p<0.05) body weight, greater (p<0.05) % body fat, and lower (p<0.05) % body lean mass vs. Con.Fasting glucose (mg/dL) was greater (p<0.05) in both S‐Mg (259±42) and L‐Mg (278±42) vs. Con (133±39), but reduced in H‐Mg (183±42) similar to Con levels. Insulin concentration (ng/mL) was greater (p<0.05) at fasting and 30 min post glucose administration (1g glucose /kg, i.p.) in all groups (L‐Mg;1.43±0.14, S‐Mg;1.05±0.17, H‐Mg;1.05±0.14) vs. Con (0.39±0.14). There was a trend (p=0.08) for greater fasting insulin levels in L‐Mg vs. H‐Mg.Glucose tolerance, estimated by area under the curve during a glucose tolerance test (glucose mg / dL), was impaired (p<0.05) in all groups (L‐Mg;22676±2279, S‐Mg;24069±2279, H‐Mg;20433±2437) vs. Con (12454±2279). Insulin sensitivity, estimated by area under the curve during an insulin tolerance test (glucose mg / dL), demonstrated significant (p<0.05) insulin resistance in L‐Mg (12394±2344) vs. Con (3866±2344), a trend (p=0.052) toward greater insulin resistance in S‐Mg (10429±2193) vs. Con. However insulin sensitivity was normalized in H‐Mg (7838±2344) vs. Con. Insulin sensitivity as evaluated by the QUICKI index indicated that all groups were insulin resistant (p<0.05) compared to Con (0.585±0.14). However, L‐Mg (0.403±0.15) had greater (p<0.05) insulin resistance than S‐Mg (0.462±0.17) and H‐Mg (0.454±0.15).Our study demonstrated that low dietary Mg intake reduces metabolic rate and worsens insulin sensitivity during diabetes. Supplemental Mg can reduce fasting glucose and improve insulin tolerance, however, the potential effect on overall insulin sensitivity during diabetes remains unclear and requires greater experimental numbers to elucidate. We conclude that this preclinical model underscores the importance of maintaining adequate Mg intake during diabetes, and provides proof of concept for initiating clinical trials to supplement Mg in patients with diabetes that have low Mg status.Support or Funding InformationThis work was supported by a research grant from Albion Labs.