Does metformin increase the serum total homocysteine level in non‐insulin‐dependent diabetes mellitus?

Hoogeveen, Ellen K.; Kostense, Piet J.; Jakobs, Cornelis; Bouter, Lex M.; Heine, R.J.; Stehouwer, Coen D.A.

doi:10.1046/j.1365-2796.1997.00231.x

Cited by 57 publications

(51 citation statements)

References 35 publications

(51 reference statements)

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“…Carlsen et al (49) reported that metformin therapy was associated with increased tHcy levels in nondiabetic subjects with cardiovascular disease. However, we found no significant difference between plasma tHcy concentrations in metformin-treated and non-metformintreated diabetic patients, in accordance with Hoogeveen et al (50).…”

Section: Homocysteine In Type 2 Diabetessupporting

confidence: 93%

Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance.

et al. 2000

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Abbreviations: BP, blood pressure; HOMA, homeostasis model assessment; HPLC, high-performance liquid chromatography; SAH, S-adenosyl-L-homocysteine; S I , insulin sensitivity index; tHcy, total homocysteine.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Hyperhomocysteinemia in Type 2 DiabetesRelationship to macroangiopathy, nephropathy, and insulin resistanceOBJECTIVE -The aim of this study was to determine the distribution of plasma total homocysteine (tHcy) concentrations in type 2 diabetic patients and to assess whether high tHcy values were related to chronic complications (particularly macroangiopathy and nephropathy) and/or the degree of insulin resistance.RESEARCH DESIGN AND METHODS -Fasting tHcy levels were measured in 122 type 2 diabetic patients in whom the presence of chronic complications (e.g., macroangiopathy, microalbuminuria, macroproteinuria, decreased creatinine clearance, hypertension, retinopathy, and neuropathy) was recorded alongside an assessment of insulin resistance by the homeostasis model assessment (HOMA).RESULTS -We found that 31% of the cohort (group 1) had raised tHcy (mean ± 1 SD) values (20.8 ± 5.1 µmol/l), whereas 69% (group 2) had normal values (10.2 ± 2.0 µmol/l). The prevalence of macroangiopathy was higher in group 1 than in group 2 subjects (70 vs. 42%, P Ͻ 0.01); the prevalence of coronary artery disease was particularly higher in group 1 (46 vs. 21%, P Ͻ 0.02). The prevalence of impaired renal function, evidenced by decreased creatinine clearance, was higher in group 1 (32 vs. 10%, P Ͻ 0.005). Other clinical and biological characteristics of both groups were comparable, although group 1 had lower levels of folic acid than group 2 (5.2 ± 2.9 vs. 7.0 ± 3.4 ng/ml, P Ͻ 0.01). No differences were found for microalbuminuria (33 vs. 31%), retinopathy (45 vs. 42%), or neuropathy (70 vs. 59%) between groups 1 and 2, respectively. The degree of insulin resistance was similar in groups 1 and 2 (46 ± 21 and 42 ± 20% of HOMA-insulin sensitivity) as was the assessment of ␤-cell function (63 ± 28 and 65 ± 46%, respectively). No differences in tHcy levels were found between subjects receiving metformin and those not receiving metformin. In contrast, the plasma tHcy level was higher in diabetic patients treated with fibrates (P = 0.0016).CONCLUSIONS -Elevated plasma tHcy levels in type 2 diabetes is associated with a higher prevalence of macroangiopathy and nephropathy when assessed from creatinine clearance indexes and is not associated with different degrees of insulin resistance.

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Section: Homocysteine In Type 2 Diabetessupporting

confidence: 93%

Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance.

et al. 2000

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“…Several previous studies reported that metformin has no effect on homocysteine or small effect, if any [4, [25][26][27]. However, patients using metformin without vitamin B 12 supplementation in the present study showed high prevalence of vitamin B 12 deficiency.…”

Section: Resultscontrasting

confidence: 58%

Screening the Effect of Metformin on Serum Vitamin B12 and Blood Homocysteine Levels in Patients with Type 2 Diabetes Mellitus

Osama¹,

Hussein²,

Abdelrahim³

et al. 2016

Med-Science

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“…Even after further adjustment for past history of cardiovascular events and intake of metformin, one of the Table 3 Correlations with serum total homocysteine concentration level in diabetics and non-diabetic subjects according to multiple regression analysis important agents affecting tHcy [33], all the above results were basically unchanged (data were not shown).…”

Section: Resultsmentioning

confidence: 97%

Factors associated with serum total homocysteine level in type 2 diabetes

Masuda

Kubo²,

Kokaze

et al. 2008

Environ Health Prev Med

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Objectives The aim of this study was to investigate the determinants of serum total homocysteine level (tHcy) in patients with type 2 diabetes mellitus (DM) according to sex. Methods A total of 1,276 Japanese, diabetics (n = 280) with a control group of non-diabetics (n = 996), were enrolled into the study from 2003 to 2005. This crosssectional study was conducted for all the subjects, using personal data regarding clinical characteristics and lifestyle. Multiple regression analysis was performed to analyze the association of tHcy with selected factors. Results In diabetic subjects, estimated glomerular filtration rate (eGFR) and serum creatinine levels (Cre), even those within the normal range, were strongly associated with tHcy after adjustment in both sexes; the standardized partial regression coefficient of eGFR for tHcy was -0.251, (p = 0.001) in diabetic men and -0.523, (p \ 0.001) in diabetic women. Furthermore, the eGFR of the diabetics, except patients with nephropathy, also had significant association with tHcy in both sexes. Fasting plasma glucose levels and serum triglyceride levels were strongly associated with tHcy in diabetic men only. HbA1c was also associated with tHcy in diabetic men only, though not as significantly. Age and presence of hypertension were significantly associated with tHcy in women. Conclusions This study suggests that there are some differences in the factors associated with tHcy between diabetics and non-diabetics, and between the sexes. There is, therefore, circumstantial evidence that elevated tHcy should be evaluated clinically. Because tHcy was strongly associated with eGFR and Cre, even within the normal ranges, tHcy may have important implications regarding the microangiopathy of the kidney and atherosclerosis.

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Does metformin increase the serum total homocysteine level in non‐insulin‐dependent diabetes mellitus?

Cited by 57 publications

References 35 publications

Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance.

Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance.

Screening the Effect of Metformin on Serum Vitamin B12 and Blood Homocysteine Levels in Patients with Type 2 Diabetes Mellitus

Factors associated with serum total homocysteine level in type 2 diabetes

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