TY - JOUR
T1 - Oral magnesium supplementation does not affect insulin sensitivity in people with insulin-treated type 2 diabetes and a low serum magnesium
T2 - a randomised controlled trial
AU - Drenthen, Linda C.A.
AU - de Baaij, Jeroen H.F.
AU - Rodwell, Laura
AU - van Herwaarden, Antonius E.
AU - Tack, Cees J.
AU - de Galan, Bastiaan E.
N1 - Funding Information:
The authors thank all volunteers for their participation. The authors thank M. Ajie (Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands) and E. Bakker (Department of Physiology, Radboudumc, Nijmegen, the Netherlands) for their assistance with analysing CGM data and activity tracker data, respectively. The authors also thank E. J. Abbink (Department of Internal Medicine, Radboudumc, Nijmegen, the Netherlands) and L. J. Oost (Department of Physiology, Radboudumc, Nijmegen, the Netherlands) for their comments on the protocol, and E. J. Abbink and the research nurses from the Radboudumc Technology Center Department of Clinical Studies, Radboudumc, Nijmegen, the Netherlands, for assistance during the clamps. The individuals named above, and the research nurses, received no financial support for their participation. Some of the data was presented as an abstract at the EASD annual meeting in 2023.
Publisher Copyright:
© 2023, The Author(s).
PY - 2024/1
Y1 - 2024/1
N2 - Aims/hypothesis: Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. Methods: Using a randomised, double-blind (both participants and investigators were blinded to the participants’ treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age =18 years, BMI 18–40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium =0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic–euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. Results: We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg-1 min-1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. Conclusions/interpretation: Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. Trial registration: EudraCT number 2021-001243-27. Funding: This study was supported by a grant from the Dutch Diabetes Research Foundation (2017–81–014). Graphical Abstract: [Figure not available: see fulltext.].
AB - Aims/hypothesis: Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. Methods: Using a randomised, double-blind (both participants and investigators were blinded to the participants’ treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age =18 years, BMI 18–40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium =0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic–euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. Results: We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg-1 min-1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. Conclusions/interpretation: Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. Trial registration: EudraCT number 2021-001243-27. Funding: This study was supported by a grant from the Dutch Diabetes Research Foundation (2017–81–014). Graphical Abstract: [Figure not available: see fulltext.].
KW - Euglycaemic clamp
KW - Insulin resistance
KW - Insulin sensitivity
KW - Magnesium supplementation
KW - Type 2 diabetes mellitus
U2 - 10.1007/s00125-023-06029-9
DO - 10.1007/s00125-023-06029-9
M3 - Article
SN - 0012-186X
VL - 67
SP - 52
EP - 61
JO - Diabetologia
JF - Diabetologia
IS - 1
ER -