[The abnormal reaction to post methionine loading test in type diabetes with or without retinopathy].
OBJECTIVE
To investigate the reaction of patients with type 2 diabetes mellitus (DM) with retinopathy (DR) or without retinopathy (NDC) to post methionine loading (PML) test, the value of PML test to identify hyperhomocystenemia (Hhcy), and the possible mechanism of vascular damages caused by Hcy.


METHODS
Solution of methione was given orally to 17DR patients, 15 NDC patients, and 28 normal controls. The plasma fasting homocysteine (Fhcy) level and the Hcy levels 4 hours after PML test (Phcy) of these subjects were measured by fluorescence polarization immunoassay (FPIA) before and 4 hours after PML test. The levels of fasting plasma folic acid and vitamin B(12) were tested by radioimmunoassay. PCR-RFLP was used to test the mutation of methelene tetrahydrofolate reductase (MTHFR) C6671. BMI, HbA1c, FBG, PBG, BUN, Cr, Ch and TG were also detected. The final metabolites of NO were determined by Griess method.


RESULTS
The levels of BMI, HbA1c, FBG and PBG in DM group and NDC group were higher than those in the control group (P < 0.05). The Fhcy levels were 13.87 micro mol/L and 11.6 +/- 1.3 micro mol/L in DR and NDC groups respectively, both higher than that in control group (8.85 micro mol/L, both P < 0.05). The Phcy was 37.3 +/- 1.3 micro mol/L in DR group and was 25.03 micro mol /L in NDC group, both higher than that in the control group (22.65 micro mol/ L, both P < 0.05). The difference between Fhcy and Phcy (Dhcy) was 24.36 micro mol/L in DR group and was 14.26 micro mol/L in NDC group, both significantly higher than that in the control group (15.07 micro mol/L, both P < 0.05). The proportion of BB genetype of MTHFR in DR group (9/17) was higher than those in NDC group (5/28) and control group (2/15). The number of Hhcy patients diagnosed by the level of Fhcy was 9 before PML test and became 15 after PML test diagnosed by the level of Phcy (P < 0.05). The whole prevalence of Hhcy in DR group was higher than that in NDC group, both the prevalence of Hhcy in DR group and the prevalence of Hhcy in NDC group were higher than those in CON group (P < 0.001). The levels of fasting metabolite of NO were 5.4 +/- 1.8 micro mol/L, 5.4 +/- 1.8 micro mol/L, and 3.4 +/- 1.7 micro mol/L in DR group, NDC group, and control group respectively. The levels of metabolits of NO after meal were 25.0 +/- 2.3 micro mol/L, 15.0 +/- 2.3 micro mol/L, and 10.4 +/- 2.0 micro mol/L in DR group, NDC group, and control group respectively. The differences between DR group and control group were statistically significant (P < 0.05). The correlation coefficient of metabolites of NO to Hcy was 0.744 (P < 0.001).


CONCLUSIONS
Patients with diabetes mellitus, especially those with retinopathy, had abnormal reaction to PML test, which may be related to higher BB genetype of MTHFR and dysfunction of insulin. PML test can be used to identify more Hhcy patients. Disturbance of NO metabolism may be one of the mechanisms of the vascular damages caused by Hcy.
Guo
Qinghua
Q
Department of Endocrinology, General Hospital of People's Liberation Army, Beijing, China.
Lu
Juming
J
Pan
Changyu
C
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000201:enzymology; D003930:Diabetic Retinopathy / Q000097:blood* / Q000209:etiology; D005215:Fasting; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation; D009566:Nitrates / Q000097:blood; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D013997:Time Factors
D009566:Nitrates; D006710:Homocysteine; D008715:Methionine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)