Fasting and post—methionine load homocyst(e)ine values are correlated with microalbuminuria and could contribute to worsening vascular damage in non—insulin-dependent diabetes mellitus patients

Lanfredini, M; Fiorina, Paolo; Peca, Maria Grazia; Veronelli, Annamaria; Mello, Ana Paula de Queiroz; Astorri, E; Dall'Aglio, P; Craveri, A

doi:10.1016/s0026-0495(98)90344-4

Cited by 55 publications

(31 citation statements)

References 30 publications

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“…When subjects in both groups with creatinine clearance Ն50 ml/min were combined and divided according to whether they were treated with fibrates (23%) or not (77%), higher tHcy levels were found in fibrate-treated patients than in non-fibrate-treated patients (17 ± 5 vs. 13 ± 6 µmol/l, P = 0.0016). However, folic acid and vitamin B 12 were comparable (6.3 ± 4.0 vs. 6.5 ± 4.0 ng/ml and 460 ± 202 vs. 582 ± 393 µg/ml, respectively). The prevalence of macroangiopathy (36 vs. 47%) and coronary (28 vs. 28%) and peripheral (8 vs. 21%) vascular disease were not significantly different in both fibrate-treated and non-fibrate-treated groups.…”

Section: Results -mentioning

confidence: 86%

“…HbA 1c levels were determined by ion-exchange HPLC. Vitamin B 12 and folic acid levels were determined by radioimmunoassay methods, as were plasma insulin and C-peptide concentrations.…”

Section: Assaysmentioning

confidence: 99%

“…Similarly, in type 1 and 2 diabetes, it is associated with established nephropathy, particularly when the latter is defined according to filtration indexes (6,14,(16)(17)(18). However, the relationship between hyperhomocysteinemia and both microalbuminuria and albuminuria is more problematic, with positive correlations being observed by several authors (8,11,12) but not confirmed by others (6,7,14,16). Our own data show that patients with hyperhomocysteinemia have a significantly higher prevalence of impaired renal function (as measured by creatinine clearance) than subjects with normal tHcy levels, while there was no difference when microalbuminuria or albuminuria was used as a surrogate marker of impaired renal function.…”

Section: Conclusion -mentioning

confidence: 99%

“…Although type 2 diabetes is definitely associated with premature atherosclerosis (4,5), only a handful of studies have dealt with the association between hyperhomocysteinemia and macro-or microangiopathic complications (6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Plasma tHcy can be affected by both glomerular hyper-and hypofiltration, two conditions not uncommon in type 2 diabetes that can respectively decrease and increase the tHcy value (6,16,17).…”

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confidence: 99%

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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: Results -mentioning

confidence: 86%

“…HbA 1c levels were determined by ion-exchange HPLC. Vitamin B 12 and folic acid levels were determined by radioimmunoassay methods, as were plasma insulin and C-peptide concentrations.…”

Section: Assaysmentioning

confidence: 99%

Section: Conclusion -mentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2000

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“…For example, in the Hoorn Study (a population-based survey of glucose tolerance and cardiovascular risk factors) (9), higher levels of tHcy were associated with microalbuminuria independent of other determinants, including the presence of type 2 diabetes and serum creatinine (Scr). Similarly, Lanfredini et al (10) found increased levels of tHcy in patients with type 2 diabetes and microalbuminuria but not in patients with type 1 diabetes who did not have overt nephropathy.…”

mentioning

confidence: 89%

The Relationship Among Homocysteine, Creatinine Clearance, and Albuminuria in Patients With Type 2 Diabetes

et al. 2001

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OBJECTIVE—Although it is accepted that elevated plasma homocysteine (tHcy) levels occur in end-stage renal disease and type 2 diabetes, the changes with milder renal dysfunction (e.g., microalbuminuria) are less clearly established. This study explores the relationship among tHcy, creatinine clearance (Ccr), and albumin excretion rate (AER) in a population with type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 260 patients with type 2 diabetes were screened in our outpatient clinic during 10 months. Fasting blood samples were collected, and AER was calculated from an overnight timed urine sample. Ccr was calculated using the Cockroft-Gault formula. RESULTS—A total of 198 subjects (76%) had normoalbuminuria (<20 μg/min), 50 subjects (19%) had microalbuminuria (20–200 μg/min), and 12 subjects (5%) had macroalbuminuria (≥200 μg/min). Those with microalbuminuria had higher levels of tHcy than those with normoalbuminuria (13.2 ± 7.8 vs. 11.3 ± 4.6 μmol/l, P < 0.05). Patients were then subdivided based on low Ccr (<80 ml · min−1 · 1.73 m−2) and normal Ccr (≥80 · min −1 · 1.73 m−2). None of the patients with macroalbuminuria had normal Ccr. In those with normoalbuminuria, tHcy levels were higher than in those with low Ccr than in those with normal Ccr (12.0 ± 4.6 vs. 10.0 ± 4.4 μmol/l, P < 0.01). The same was found for those with microalbuminuria (low Ccr versus normal Ccr: 14.6 ± 9.0 vs. 10.2 ± 2.8 μmol/l, P < 0.02). For normal Ccr, tHcy was similar irrespective of AER (normoalbuminuria versus microalbuminuria: 10.0 ± 4.4 vs. 10.2 ± 2.8 μmol/l, NS). For low Ccr, tHcy was higher in those with microalbuminuria versus normoalbuminuria (14.6 ± 9.0 vs. 12.0 ± 4.6 μmol/l, P = 0.01). Using multivariate regression, Ccr, but neither AER nor the presence of albuminuria, was an independent predictor of tHcy. CONCLUSIONS—These data strongly suggest that in patients with type 2 diabetes, the relationship between plasma tHcy and AER is largely due to associated changes in renal function, as defined by Ccr.

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Hyperhomocysteinemia, Diabetes, and Cardiovascular Disease

Hoogeveen¹,

Rothman²

2001

Primary and Secondary Preventive Nutrition

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Fasting and post—methionine load homocyst(e)ine values are correlated with microalbuminuria and could contribute to worsening vascular damage in non—insulin-dependent diabetes mellitus patients

Cited by 55 publications

References 30 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.

The Relationship Among Homocysteine, Creatinine Clearance, and Albuminuria in Patients With Type 2 Diabetes

Hyperhomocysteinemia, Diabetes, and Cardiovascular Disease

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