Hypomagnesaemia in Type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control

Diabetologia, Jan 1992

Ch. Schnack, I. Bauer, P. Pregant, P. Hopmeier, G. Schernthaner

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Hypomagnesaemia in Type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control

Diabetologia Hypomagnesaemia in Type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control Ch. Schnack 0 I. Bauer t P. Pregant 0 R Hopmeier G. Schernthaner 0 0 Department of Medicine I and 2 Institute of Clinical Chemistry, Rudolfstiftung Hospital , Vienna , Austria Summary. Low levels of magnesium have frequently been reported in diabetes mellitus especially in poorly controlled Type I (insulin-dependent) diabetic patients. Furthermore hypomagnesaemia might contribute to insulin resistance in Type 2 (non-insulin-dependent) diabetes. As the influence of improved metabolic control on plasma magnesium levels is unknown in Type 2 diabetic patients we studied magnesium plasma levels in 50 patients 1)before, 2 ) o n e and 3) three months after the initiation of insulin therapy or intensified treatment with oral hypoglycaemic agents. Magnesium plasma levels were measured by a colorimetric method and were significantly reduced in diabetic patients compared to healthy control subjects (0.79 + 0.01 mmol/1 vs 0.88 + 0.01 mmol/1; p < 0.0001). Metabolic control was significantly improved as documented by reduced HbAlc levels in both in- Diabetes mellitus; Type 2 (non-insulin-dependent) diabetes; insulin resistance; magnesium; electrolytes 9 Springer-Verlag 1992 R e d u c e d magnesium plasma levels have frequently b e e n r e p o r t e d in b o t h Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients [ 1-5 ]. A n inverse relationship b e t w e e n metabolic control and plasma magnesium levels was found in Type i diabetic patients and has b e e n attributed to increased urinary magnesium losses [ 2, 3 ]. In Type 2 diabetic patients however, hypomagnesaemia can be both a consequence or a cause of increased insulin resistance [5]. T h e fact, that chronic magnesium supplements in Type 2 diabetic patients improves both islet Beta-cell response and insulin action [ 6, 7 ] favours the hypothesis that hypomagnesaemia is closely related to insulin resistance in these patients. It has b e e n suggested that Type 2 diabetic patients may benefit from chronic therapeutic administration of magnesium salt [ 6, 7 ]. On the other hand it is not known w h e t h e r imp r o v e m e n t of metabolic control per se and/or insulin t h e r a p y corrects hypomagnesaemia in these patients. We t h e r e f o r e studied the influence of improved diabetes control with either (a) initiation of insulin substitution or (b) intensified t r e a t m e n t with strict diet and oral hypoglycaemic agents on plasma magnesium levels in sulin-treated patients or the patients on oral hypoglycaemic agents (p < 0.003). However, plasma magnesium levels remained unchanged during the follow-up in the insulintreated group (1:0.79 + 0.02 mmol/1; 2:0.81 + 0.02 mmol/1; 3:0.79 + 0.01 mmol/1) as well as in the patients on oral hypoglycaemic agents (1:0.79 + 0.03 mmol/1; 2:0.78 + 0.02 mmol/ 1; 3:0.84  0.04 mmol/1). This study shows that even marked improvement of glycaemic control does not correct hypomagnesaemia in Type 2 diabetes. We conclude that hypomagnesaemia might be related to the insulin-resistant state and that possible beneficial effect of chronic magnesium administration should be evaluated in these patients. 50 Type 2 diabetic patients with insufficient glycaemic control. Subjects and methods The study was performed in 50 Type 2 diabetic patients (21 males and 29 females; age 61 + 11 years, diabetes duration 11 + 8 years, HbAlc 10.5+ 1.8relative %; mean + SD) with insufficient metabolic control on oral hypoglycaemic agents (OHA). Patients were hospitalized and took part in the diabetes education programme of our unit. In 35 patients insulin treatment was started, whereas in 15 patients good metabolic control was achieved by continuation of OHA treatment due to maximal dietary efforts. None of the patients had marked renal damage or had taken magnesium drugs or hypotensive diuretics. The diet was kept constant throughout the whole study period (treatment of hypoglycaemic attacks excluded), noncompliant subjects were excluded. The control group consisted of 50 healthy subjects matched for age and sex. Blood samples were taken the morning after overnight fasting and were repeated one month and three months after the start of medical treatment in the clinic outpatient department. Magnesium was measured by a colorimetric method (Xylidyl blue reaction) using an automated analysis system (13 M Hitachi 717 Naka works Values are means  SEM ap <0.025(1vs2,1vs3,2vs3); bp <0.0005(lVS2,1VS3); Cp <0.005(lvs2,1VS3); dp <0.0001 (lvs2,1VS3) limited, Tokyo, Japan). The correlation coefficient between the color method of our laboratory and the Atomic Absorption Spectrophotometry was r = 0.97 (p < 0.0001). Blood glucose, lipids and routine clinical parameters were determined by a parallel analyser. HbAlc was measured by HPLC. Statistical analysis Statistical analysis was performed using the analysis of variance procedure with correction for multiple measurements using the SAS program. Data are expressed as means  unless otherwise stated. 11 10 9 8 7" / 0,9 O,8 0,7 I _ _ t T h e m a i n finding o f t h e p r e s e n t s t u d y is, t h a t p l a s m a m a g n e s i u m levels are significantly r e d u c e d in T y p e 2 diabetic p a t i e n t s a n d are n o t i n f l u e n c e d b y i m p r o v e m e n t o f m e t a bolic control. A s r e p o r t e d p r e v i o u s l y [ 8 ] we f o u n d n o c o r r e l a t i o n bet w e e n t h e H b A l c a n d fasting b l o o d glucose c o n c e n t r a tions a n d p l a s m a m a g n e s i u m levels in T y p e 2 diabetic patients, w h e r e a s in T y p e 1 diabetic patients a c o r r e l a t i o n b e t w e e n the fasting b l o o d glucose a n d s e r u m m a g n e s i u m was o b s e r v e d [ 8 ]. T h e s e results indicate t h a t in c o n t r a s t to T y p e i diabetic p a t i e n t s [ 2, 4, 10 ] h y p o m a g n e s a e m i a in T y p e 2 diabetic p a t i e n t s is n o t directly c o r r e l a t e d to m e t a bolic control. Ch. Schnack et al.: Hypomagnesaemiain Type 2 diabetes We have further shown that even m a r k e d i m p r o v e m e n t of metabolic control as d o c u m e n t e d by a significant reduction of H b A l c and fasting b l o o d glucose levels has no effect on the reduced p l a s m a m a g n e s i u m levels in Type 2 diabetes, in spite of w h e t h e r patients receive insulin t h e r a p y or intensified t r e a t m e n t with strict diet and O H A . In fact, it was recently shown, that h y p o m a g n e s a e m i a not only occurs in Type 2 diabetic patients [ 1, 4, 5, 8 ] but also in patients with essential hypertension [ 9, 11 ]. Furthermore, Type 2 diabetes, aging and essential hypertention [ 5, 10-12 ], classic conditions associated with insulin resistance are associated with an impaired insulin mediated accumulation of m a g n e s i u m into erythrocytes [ 9, 13 ]. In vitro it was shown, that even high levels of insulin cannot correct the reduced m a g n e s i u m shift into erythrocytes from insulin-resistant Type 2 diabetic patients with hypom a g n e s a e m i a , which might be explained by a post-receptor defect [ 5 ]. In diabetic patients h y p o m a g n e s a e m i a might r e p r e s e n t an i n d e p e n d e n t risk factor for cardiovascular complications [ 14, 15 ]. Recently it was shown, that chronic m a g n e sium administration might i m p r o v e the insulin response and insulin action in insulin-resistant Type 2 diabetic patients [ 6, 7 ]. Recently [ 16 ] chronic m a g n e s i u m s u p p l e m e n t a t i o n has b e e n discussed as a possible beneficial therapeutic app r o a c h increasing b o t h insulin secretion and insulin sensitivity in Type 2 diabetic patients. Since h y p o m a g n e s a e m i a persists even after m a r k e d i m p r o v e m e n t of glycaemic control the effects of m a g n e s i u m administration should be evaluated in Type 2 diabetic patients in long-term studies. Acknowledgements. This study was made possible by the expert assistance of A. Bergen and K. Meyer. The secretarial assistance of S.Singer and G. Harringer is also gratefully acknowledged. Financial support for this study was provided by the "Jubil~iumsfond der Osterreichischen Nationalbank', project No 3434. 1. Mather HM , Nisbet JA , Burton GH et al. ( 1979 ) Hypomagnesaemia in diabetes . Clin Chim Acta 95 : 235 - 242 2. McNair R Christensen MS , Christiansen C , Modshod S , Transbol IB ( 1982 ) Renal hypomagnesaemia in human diabetes mellitus: its relation to glucose homeostasis . Eur J Clin Invest 12 : 81 - 85 3. Ponder SW , Brouhard BH , Travis LB ( 1990 ) Hyperphosphaturia and hypermagnesuria in children with IDDM . Diab Care 13 : 437 - 441 4. Sj6gren A , Floren CH , Nilsson A ( 1988 ) Magnesium potassium and zinc deficiency in subjects with type I and type II diabetes . Acta Med Scand 224 : 461 - 465 5. Paolisso G , Sgambato S , Giugliano D et al. ( 1988 ) Impaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in Type-2 (non-insulin-dependent) diabetic patients . Diabetologia 31 : 910 - 915 6. Paolisso G , Passariello N , Pizza G et al. ( 1989 ) Dietary magnesium supplements improve B-cell response to glucose and arginine in elderly non-insulin dependent diabetic subjects . Acta Endocrinol 121 : 16 - 20 7. Paolisso G , Sgambato S , Pizza G , Passariello N , Varricchio M , D'Onofrio F ( 1989 ) Improved insulin response and action by chronic magnesium administration in aged NIDDM subjects . Diab Care 12 : 265 - 269 8. Prager R , Schernthaner G , Kostner G , Miihlhauser I , Meisinger V ( 1982 ) Hypomagnesi~mie bei Diabetes melfitus . Korrelationsanalysen mit Stoffwechselkontrollgrad, Lipidstatus und Thrombozytenfunktion. Akt Endokrin Stoffw 3 : 140 - 143 9. Paolisso G , Passariello N , Sgambato Set al. ( 1987 ) Impaired insulin-mediated erythrocyte magnesium accumulation in essential hypertension . Clin Sci 73 : 535 - 539 10. Fink RI , Kolterman OG , Griffin J , Olefsky JM ( 1983 ) Mechanisms of insulin resistance in aging . J Clin Invest 71 : 1523 - 1535 11. Rowe JW , Minaker KL , Pallotta JA , Flier JS ( 1983 ) Characteristics of the insulin resistance of aging . J Clin Invest 71 : 1581 - 1587 12. Ferrannini E , Buzzigoli G , Bonadonna R et al. ( 1987 ) Insulin resistance in essential hypertension . N Engl J Med 317 : 350 - 357 13. Paolisso G , Sacchettino A , Sgambato S , Gentile S , Varicchio M , D'Onofrio F ( 1988 ) Impaired insulin-mediated erythrocyte magnesium accumulation in the elderly . Diab Nutr Metab 1 : 215 - 219 14. Seelig MS , Heggtveit HA ( 1974 ) Magnesium interrelationship in ischemic heart disease: a review . Am J Clin Nutr 27 :5% 79 15. Mather HM , Levin GE , Nisbet JA ( 1982 ) Hypomagnesaemia and ischemic heart disease in diabetes . Diab Care 5 : 452 - 463 16. Paolisso G , Scheen A , D'Onofrio E Lef~bvre P ( 1990 ) Magnesium and glucose homeostasis . Diabetologia 33 : 511 - 514 Received: 11 July 1991 and in revised form: 19 September 1991


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Ch. Schnack, I. Bauer, P. Pregant, P. Hopmeier, G. Schernthaner. Hypomagnesaemia in Type 2 (non-insulin-dependent) diabetes mellitus is not corrected by improvement of long-term metabolic control, Diabetologia, 1992, 77-79, DOI: 10.1007/BF00400855