OBJECTIVE—Homocysteine is an emerging risk factor for cardiovascular and nondiabetic ocular vaso-occlusive diseases. However, studies of the relationship between homocysteine and diabetic retinopathy have reported inconsistent results. The purpose of this study was to evaluate the relationship between plasma total homocysteine concentration and diabetic retinopathy.

RESEARCH DESIGN AND METHODS—We assessed the homocysteine-retinopathy relationship in 168 men and women with type 2 diabetes in a community-based, cross-sectional study. We photodocumented diabetic retinopathy status and measured plasma total homocysteine concentration using a commercial fluorescence polarization immunoassay enzymatic kit. Data for selected clinical/demographic variables and established risk factors for diabetic retinopathy were obtained from fasting blood samples and an interviewer-assisted lifestyle questionnaire.

RESULTS—A higher mean plasma total homocysteine concentration was observed in diabetic individuals with retinopathy than in those without retinopathy (11.5 μmol/l [95% CI 10.4–12.5] vs. 9.6 μmol/l [9.1–10.2], P = 0.001). Furthermore, the relationship between homocysteine and diabetic retinopathy was not explained by renal dysfunction and was independent of the other major risk factors for diabetic retinopathy (duration of diabetes, A1C, and systolic blood pressure) and determinants of higher homocysteine concentrations (age, sex, and red cell folate) (odds ratio 1.20 [95% CI 1.023–1.41], P = 0.024).

CONCLUSIONS—Plasma total homocysteine concentration may be a useful biomarker and/or a novel risk factor for increased risk of diabetic retinopathy in people with type 2 diabetes.

Homocysteine has generated considerable interest in recent years as both a sensitive biomarker of folate deficiency and an emerging risk factor for cardiovascular disease (even within the normal range of homocysteine concentrations) (1) and has been linked to vaso-occlusive diseases in the eye (2). The known determinants of higher fasting plasma homocysteine levels are older age, male sex, and certain genetic abnormalities, while the major risk factors for hyperhomocysteinemia (elevated plasma total homocysteine concentration) are impaired renal function and poor vitamin B status (particularly folate status but also vitamin B6 and B12 status). In the elderly (age >75 years), hyperhomocysteinemia is generally associated with low folate status or renal impairment (3).

In addition, a multitude of physiological, lifestyle, and drug associations with higher homocysteine concentrations have been reported, including positive associations with smoking and alcohol and coffee intake (4). Numerous studies have evaluated the diabetic retinopathy–homocysteine relationship (Table 1) but have yielded inconsistent results (528), possibly as a result of methodological differences and residual confounding. We hypothesized that homocysteine is associated with diabetic retinopathy in type 2 diabetes, independent of the major determinants of both retinopathy and homocysteine levels, and that homocysteine concentrations would be higher in diabetic individuals with than in those without retinopathy.

Diabetes status and subject selection.

Self-reported diabetes status was confirmed biochemically according to World Health Organization diagnostic criteria for classification of diabetes (29). To broaden the range of dietary intakes and lifestyle exposures, we sourced subjects from the Melbourne Collaborative Cohort Study (MCCS), a community-based prospective cohort of 41,528 male and female volunteers aged 40–69 years at baseline (1989–1994) and recruited from the electoral roll, ethnic radio, clubs, and churches (30). We invited 248 men and women with type 2 diabetes from the MCCS to participate in this study, of whom we excluded three (two men with type 1 diabetes and one man with ungradable photographs). Of the eligible subjects (n = 245), 68% (n = 168) participated in the study. Ethics approval was obtained from the MCCS scientific committee, Deakin University, and Monash University (Melbourne, Australia), and written informed consent was obtained from every participant.

Diabetic retinopathy.

We used a mydriatic retinal fundus camera (Kowa FX-500S; Kowa, Tokyo, Japan) to photodocument retinal status. Diabetic retinopathy grading was based on the EURODIAB protocol (validated against the Airlie House classification), in which the overall grading was that of the worse eye and nonproliferative diabetic retinopathy was defined as more than one microaneurysm and/or hemorrhage (31). A medical retina specialist (C.A.H.), masked to all other participant information, graded the slides on two separate occasions to assess internal validity, and agreement between gradings was excellent (κ value of 0.986).

Clinical measures and retinopathy risk factors.

Systolic and diastolic blood pressure was recorded using a Dinamap XL portable automated adult vital signs monitor (model 9300; Critikon, Tampa, FL). Blood pressure was recorded as the average of the last two of three consecutive readings, obtained from the right arm of seated subjects at 1-min intervals after a 10-min rest period. Weight was measured to within 0.1 kg before breakfast and following a 12-h fast, with subjects wearing light clothing and no shoes, using digital electronic scales (UC-300; A.N.D, Tokyo, Japan). Height was measured to within 0.1 cm using a wall-mounted stadiometer (Harpenden; Holtain Limited, Crymych, U.K.). BMI was calculated as weight in kilograms divided by the square of height in meters (2). A current smoker was defined as a subject who smoked at least seven cigarettes a week at the time of completing the questionnaire.

Plasma biochemistry.

Homocysteine concentration in EDTA-treated plasma was assayed using a commercially available Fluorescence Polarization Immunoassay (Abbott Diagnostics, Abbott Park, IL) (32). Plasma total homocysteine concentrations were read on an IMx System Analyser (Abbott Diagnostics). Plasma glucose concentrations were analyzed using an automatic analyzer (model 705; Hitachi, Tokyo, Japan) and a commercial enzymatic kit (Boehringer Mannheim Diagnostica, Mannheim, Germany) by the glucose oxidase method. Plasma cholesterol and triacylglycerol concentrations were also analyzed with the Hitachi model 705 analyzer using a commercial enzymatic kit (Boehringer Mannheim Diagnostica).

Erythrocyte folate concentration.

Erythrocyte folate was measured in hemolyzed whole blood (1/22 dilution) using a Bio-Rad Quantaphase Folate radioassay (detection range: 0.2–3.0 ng/ml, coefficients of variation [CVs] 9.8–12.1%) (33). Red cell folate concentration was calculated as follows: red cell folate (adjusted) = (22 × unadjusted red cell folate concentration)/hematocrit.

Urinary biochemistry.

Urinary albumin concentration was measured using immunonephelometry (Kallestadt QM300 or Beckman 360 Array nephelometers; interassay CV 3–5%). Urinary creatinine concentration was measured using an alkaline picrate method (Olympus AU800 autoanalyzer; interassay CV 2%). The urinary albumin-to-creatinine ratio (ACR) was then calculated as albumin (milligrams)/creatinine (millimoles).

Statistical analyses.

We used SPSS software for Windows (version 13; SPSS, Chicago, IL) to perform statistical analyses. The data were cross-sectional observations. Descriptive statistics for the exposure and outcome variables were obtained, and variables with distributions that were not normally distributed were log transformed before analysis. Associations between retinopathy and continuous variables were assessed using ANOVA for variables with homogeneous variances or the corresponding nonparametric test when variances were nonhomogeneous. Associations between categorical variables were analyzed using χ2 tests.

Initially, variables assessed in univariate analyses, including known risk factors for diabetic retinopathy, were modeled using binomial logistic regression analysis to determine the best clinical predictors of diabetic retinopathy. Plasma total homocysteine concentration was then added to subsequent models that controlled for the major risk factors for diabetic retinopathy and the established determinants of homocysteine. The fit of each model was tested, and the Nagelkerke R2 approximation was compared for each of the logistic regression models. P < 0.05 was considered statistically significant.

Characteristics of the participants are shown in Table 2. Diabetic retinopathy was identified in 28.6% of people with type 2 diabetes. As expected, A1C level was higher in participants with than in those without retinopathy, although both groups demonstrated poor metabolic control (A1C >7%). Participants with diabetic retinopathy had a significantly longer duration of diabetes, were more likely to use hypoglycemia medication(s), and had a higher ACR. The majority in both retinopathy and nonretinopathy groups had systolic hypertension (systolic blood pressure >140 mmHg), with a trend evident for a higher systolic and pulse blood pressure in the retinopathy group. Lipid levels were not associated with diabetic retinopathy, and there were few smokers in the study population. Male sex was not associated with diabetic retinopathy (31 vs. 25% for women and men, respectively; P = 0.388), and we observed a nonsignificant sex difference in the median homocysteine concentration (9.0 vs. 9.9 μmol/l; P = 0.063).

A higher mean plasma total homocysteine concentration was observed in diabetic individuals with than in those without retinopathy (11.5 [95% CI 10.4–12.5] vs. 9.6 [9.1–10.2], respectively; P = 0.001). Hyperhomocysteinemia (plasma total homocysteine ≥12 μmol/l for a folate-fortified population) was present in 22% (n = 37) of individuals with type 2 diabetes, and 7.7% (n = 14) had a plasma total homocysteine concentration >15 μmol/l. Among those with diabetic retinopathy, 33% (n = 17) had hyperhomocysteinemia and 14.6% (n = 8) had a plasma total homocysteine concentration >15 umol/l.

In participants both with and without retinopathy, the mean red cell folate concentration was in the normal range and was not (statistically) significantly different between subjects with and without retinopathy (312 ng/ml [95% CI 252–373]) vs. 371 ng/ml [322–421], P = 0.174). However, folate depletion (red cell folate concentration <160 ng/ml) or deficiency (red cell folate concentration <120 ng/ml) was observed in 8.1% (n = 12) of participants. As expected, a higher red cell folate concentration (adjusted for hematocrit) was associated with lower homocysteine levels (r = −0.359, P < 0.0001).

Table 3 demonstrates that, of the established risk factors and clinical characteristics in Table 2, duration of diabetes and ACR ratio were the only independent predictors of diabetic retinopathy in our study group. In logistic regression models of homocysteine as a predictor of increased risk of diabetic retinopathy (Table 4), the significant association between homocysteine and diabetic retinopathy identified in univariate testing remained significant in multivariate testing (model 1). The increased risk of diabetic retinopathy predicted by higher homocysteine concentrations was not explained by renal dysfunction after controlling both for the other major risk factors for diabetic retinopathy (duration of diabetes, A1C, and systolic blood pressure) and for the other determinants of homocysteine concentrations (age, sex, and red cell folate) (odds ratio 1.20 [95% CI 1.023–1.41], P = 0.024), as shown in model 2. Model 3 demonstrates that biguanide (metformin) use did not explain the significant relationship between plasma homocysteine concentration and diabetic retinopathy. Age was inversely associated with diabetic retinopathy in the models that adjusted for systolic blood pressure.

Several interesting observations were made in this study. First, a higher plasma homocysteine concentration was associated with prevalent retinopathy in individuals with type 2 diabetes. Second, the difference in the mean plasma homocysteine concentration between subjects with and without retinopathy was relatively small (<2 μmol/l). Third, the mean plasma homocysteine concentration for both subjects with and without retinopathy was below the upper limit for normal for this age-group, i.e., 12 μmol/l for mean age <65 years (34). Finally, a 1 μmol/l increase in plasma homocysteine concentration was an independent predictor of increased risk of diabetic retinopathy of between 15 and 20% after adjusting for the established risk factors for diabetic retinopathy (duration of diabetes, A1C, and systolic blood pressure) and the major determinants of plasma total homocysteine concentration (age, sex, red cell folate concentration, and renal function).

Prospective studies are now needed to confirm our findings, which may have implications for the management of diabetes: Dietary modulation of homocysteine levels is possible (35). Interestingly, poor folate status did not account for the observed homocysteine-retinopathy relationship in our study, possibly due to the adequate folate status of the majority of participants. Future studies that evaluate the association between poor folate status and diabetic retinopathy may help clarify the basis of the observed homocysteine-retinopathy relationship.

Homocysteine may be a good biomarker for increased risk of diabetes complications, since retinopathy, nephropathy, and cardiovascular disease have all been linked to higher homocysteine levels. Our finding that a difference in homocysteine concentration of <2 μmol/l separated subjects with and without retinopathy suggests that a relatively small increase in the plasma homocysteine concentration, in the order of 1 μmol/l, may be a useful trigger for intensification of treatment of the major risk factors for diabetes complications (blood pressure, blood glucose, and blood lipids). Moreover, for the timely identification of individuals at greater risk of the vascular complications of diabetes, the upper limit of the normal range for plasma homocysteine (12 μmol/l for folate-fortified and/or adult populations and 20 μmol/l for folate-unfortified and/or older populations [age >65 years]) may need to be lowered, as has been the case for blood pressure and lipid target levels.

A limitation of many homocysteine studies, particularly homocysteine-lowering cardiovascular disease trials (36), has been their failure to control for renal disease. In the many studies that have evaluated the diabetic retinopathy–homocysteine relationship (Table 1), several did not control for impaired renal function. A number did not control for established retinopathy risk factors, and none controlled for metformin use. All of these factors were accounted for in the present study.

Many of the earlier studies evaluated homocysteine only as a categorical variable (proportion of study sample with hyperhomocysteinemia, i.e., homocysteine concentration above a designated cutoff). However, the cutoff for hyperhomocysteinemia is arbitrary and differed substantially between studies, ranging from 11.7 to 16 μmol/l. In our study, subjects with and without retinopathy had mean homocysteine levels <11 μmol/l, indicating that the cutoff used in earlier studies may have been too high. Therefore, both the variability in and the level of the selected cutoffs may have contributed to discordant findings between studies. Consequently, we evaluated the impact of homocysteine as a continuous variable.

Other methodological issues may have also contributed to the disparity between studies. Homocysteine can be determined either directly or after derivatization, making comparisons of findings between studies difficult. We measured plasma homocysteine levels directly, consistent with current expert opinion and recommendations. In addition, there are many different methods and classifications for assessment of diabetic retinopathy: we photodocumented retinopathy status according to the EURODIAB protocol, validated against the Airlie House classification, unlike many of the earlier homocysteine studies in which retinopathy was assessed using ophthalmoscopy (14). Nevertheless, it is possible that more accurate assessment of diabetic maculopathy would facilitate a better understanding of the nature of the retinopathy-homocysteine relationship.

The main limitation of this study was the use of a cross-sectional design, which precludes determination of temporal direction and therefore of causal inference. Although we controlled for retinopathy risk factors and the most important confounders of homocysteine in this population—specifically, age, sex, smoking status, red cell folate levels, metformin use, and renal status—many factors linked to homocysteine in other studies were not assessed in our study, such as genetic and lifestyle factors (e.g., vitamin B12 and B6 intakes) and conditions associated with diabetes and aging, such as depression and dementia (32). However, in contrast to earlier studies, recruiting from a community-based cohort enabled evaluation of the homocysteine-retinopathy relationship in a more health-conscious group of individuals at lower risk of comorbidities and potential confounders than hospital-based populations.

In conclusion, our observations support a role for homocysteine in diabetic retinopathy at least as a biomarker and potentially as a risk factor if prospective studies confirm our observations. While we acknowledge that there is currently insufficient evidence to recommend routine screening of homocysteine for the purpose of treating elevated homocysteine concentrations in the wider adult population, almost 1 in 10 of our participants was folate depleted and thus at risk of folate deficiency and related functional deficits, suggesting that monitoring homocysteine and folate status in people with type 2 diabetes may have net health benefits. Finally, this study provides further support for recommending a folate-rich diet based on high intakes of fresh fruit and vegetables for people with type 2 diabetes.

The National Health and Medical Research Council of Australia partly funded this study (project no. 124317), which represents the collaboration and contribution of many, especially Connie Karschimkus, Mary Kaimakamis, and Melissa Cameron.

This work would not have been possible without the Melbourne Collaborative Cohort Study and the infrastructure support provided by the Cancer Council Victoria.

1.
Weir D, Scott J; Homocysteine as a risk factor for cardiovascular and related disease: nutritional implications.
Nutr Res Rev
11
:
311
–338,
1998
2.
Coral K, Raman R, Rathi S, Rajesh M, Sulochana KN, Angayarkanni N, Paul PG, Ramakrishnan S: Plasma homocysteine and total thiol content in patients with exudative age-related macular degeneration.
Eye
20
:
203
–207,
2006
3.
Jacques PF, Bostom AG, Wilson PW, Rich S, Rosenberg IH, Selhub J: Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.
Am J Clin Nutr
73
:
613
–621,
2001
4.
Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Tverdal A, Tell GS, Nygard O, Vollset SE: The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease.
J Nutr
136
:
1731S
–1740S,
2006
5.
Chico A, Perez A, Cordoba A, Arcelus R, Carreras G, de Leiva A, Gonzalez-Sastre F, Blanco-Vaca F: Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: a new link between diabetic nephropathy and cardiovascular disease?
Diabetologia
41
:
684
–693,
1998
6.
Hultberg B, Agardh E, Andersson A, Brattstrom L, Isaksson A, Israelsson B, Agardh CD: Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus.
Scand J Clin Lab Invest
51
:
277
–282,
1991
7.
Agardh CD, Agardh E, Andersson A, Hultberg B: Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus.
Scand J Clin Lab Invest
54
:
637
–641,
1994
8.
Neugebauer S, Baba T, Kurokawa K, Watanabe T: Defective homocysteine metabolism as a risk factor for diabetic retinopathy.
Lancet
349
:
473
–474,
1997
9.
Smulders YM, Rakic M, Slaats EH, Treskes M, Sijbrands EJ, Odekerken DA, Stehouwer CD, Silberbusch J: Fasting and post-methionine homocysteine levels in NIDDM: determinants and correlations with retinopathy, albuminuria, and cardiovascular disease.
Diabetes Care
22
:
125
–132,
1999
10.
Stabler SP, Estacio R, Jeffers BW, Cohen JA, Allen RH, Schrier RW: Total homocysteine is associated with nephropathy in non-insulin-dependent diabetes mellitus.
Metabolism
48
:
1096
–1101,
1999
11.
Agardh E, Hultberg B, Agardh CD: Severe retinopathy in type 1 diabetic patients is not related to the level of plasma homocysteine.
Scand J Clin Lab Invest
60
:
169
–174,
2000
12.
Chiarelli F, Pomilio M, Mohn A, Tumini S, Vanelli M, Morgese G, Spagnoli A, Verrotti A: Homocysteine levels during fasting and after methionine loading in adolescents with diabetic retinopathy and nephropathy.
J Pediatr
137
:
386
–392,
2000
13.
Vaccaro O, Perna AF, Mancini FP, Iovine C, Cuomo V, Sacco M, Tufano A, Rivellese AA, Ingrosso D, Riccardi G: Plasma homocysteine and microvascular complications in type 1 diabetes.
Nutr Metab Cardiovasc Dis
10
:
297
–304,
2000
14.
Hoogeveen EK, Kostense PJ, Eysink PE, Polak BC, Beks PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD: Hyperhomocysteinemia is associated with the presence of retinopathy in type 2 diabetes mellitus: the Hoorn Study.
Arch Intern Med
160
:
2984
–2990,
2000
15.
Buysschaert M, Jamart J, Dramais AS, Wallemacq P, Hermans MP: Micro- and macrovascular complications and hyperhomocysteinaemia in type 1 diabetic patients.
Diabetes Metab
27
:
655
–659,
2001
16.
Agullo-Ortuno MT, Albaladejo MD, Parra S, Rodriguez-Manotas M, Fenollar M, Ruiz-Espejo F, Tebar J, Martinez P: Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus.
Clin Chim Acta
326
:
105
–112,
2002
17.
Abdella NA, Mojiminiyi OA, Akanji AO, Moussa MA: Associations of plasma homocysteine concentration in subjects with type 2 diabetes mellitus.
Acta Diabetol
39
:
183
–190,
2002
18.
Matteucci E, Rossi L, Mariani S, Fagnani F, Quilici S, Cinapri V, Giampietro O: Blood levels of total homocysteine in patients with type 1 diabetes (with no complications, diabetic nephropathy and/or retinopathy) and in their non-diabetic relatives.
Nutr Metab Cardiovasc Dis
12
:
184
–189,
2002
19.
Guo Q, Lu J, Pan C: [The abnormal reaction to post methionine loading test in type diabetes with or without retinopathy].
Zhonghua Yi Xue Za Zhi
82
:
725
–728,
2002
[article in Chinese]
20.
Yang G, Lu J, Pan C: [The impact of plasma homocysteine level on development of retinopathy in type 2 diabetes mellitus].
Zhonghua Nei Ke Za Zhi
41
:
34
–38,
2002
[article in Chinese]
21.
Looker HC, Fagot-Campagna A, Gunter EW, Pfeiffer CM, Narayan KM, Knowler WC, Hanson RL: Homocysteine as a risk factor for nephropathy and retinopathy in type 2 diabetes.
Diabetologia
46
:
766
–772,
2003
22.
Sun J, Xu Y, Zhu Y, Lu H, Deng H, Fan Y, Sun S, Zhang Y: The relationship between MTHFR gene polymorphisms, plasma homocysteine levels and diabetic retinopathy in type 2 diabetes mellitus.
Chin Med J (Engl)
116
:
145
–147,
2003
23.
Saeed BO, Nixon SJ, White AJ, Summerfield GP, Skillen AW, Weaver JU: Fasting homocysteine levels in adults with type 1 diabetes and retinopathy.
Clin Chim Acta
341
:
27
–32,
2004
24.
Goldstein M, Leibovitch I, Yeffimov I, Gavendo S, Sela BA, Loewenstein A: Hyperhomocysteinemia in patients with diabetes mellitus with and without diabetic retinopathy.
Eye
18
:
460
–465,
2004
25.
Yucel I, Yucel G, Muftuoglu F: Plasma homocysteine levels in noninsulin-dependent diabetes mellitus with retinopathy and neovascular glaucoma.
Int Ophthalmol
25
:
201
–205,
2004
26.
Soedamah-Muthu SS, Chaturvedi N, Teerlink T, Idzior-Walus B, Fuller JH, Stehouwer CD: Plasma homocysteine and microvascular and macrovascular complications in type 1 diabetes: a cross-sectional nested case-control study.
J Intern Med
258
:
450
–459,
2005
27.
de Luis DA, Fernandez N, Arranz ML, Aller R, Izaola O, Romero E: Total homocysteine levels relation with chronic complications of diabetes, body composition, and other cardiovascular risk factors in a population of patients with diabetes mellitus type 2.
J Diabetes Complications
19
:
42
–46,
2005
28.
Huang EJ, Kuo WW, Chen YJ, Chen TH, Chang MH, Lu MC, Tzang BS, Hsu HH, Huang CY, Lee SD: Homocysteine and other biochemical parameters in type 2 diabetes mellitus with different diabetic duration or diabetic retinopathy.
Clinica Chimica Acta
366
:
293
–298,
2006
29.
World Health Organization:
Diabetes Mellitus: Report of a WHO Study Group
. Geneva, World Health Org., 1999 (Tech. rep. ser. no. WHO/NCD/NCS/99.2.16)
30.
Giles GG, English DR: The Melbourne Collaborative Cohort Study.
IARC Sci Publ
156
:
69
–70,
2002
31.
Aldington SJ, Kohner EM, Meuer S, Klein R, Sjolie AK: Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM complications study.
Diabetologia
38
:
437
–444,1995
32.
Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, Johnston C, Engbaek F, Schneede J, McPartlin C, Scott JM: Facts and recommendations about total homocysteine determinations: an expert opinion.
Clin Chem
50
:
3
–32,
2004
33.
Brown RD, Jun R, Hughes W, Watman R, Arnold B, Kronenberg H: Red cell folate assays: some answers to current problems with radioassay variability.
Pathology
22
:
82
–87,
1990
34.
Hankey GJ, Eikelboom JW, Ho WK, van Bockxmeer FM: Clinical usefulness of plasma homocysteine in vascular disease.
Med J Aust
181
:
314
–318,
2004
35.
Rowley KG, Lee AJ, Yarmirr D, O’Dea K: Homocysteine concentrations lowered following dietary intervention in an aboriginal community.
Asia Pac J Clin Nutr
12
:
92
–95,
2003
36.
Coca SG, Krumholz HM, Garg AX, Parikh CR: Underrepresentation of renal disease in randomized controlled trials of cardiovascular disease.
Jama
296
:
1377
–1384,
2006

Published ahead of print at http://care.diabetesjournals.org on 26 September 2007. DOI: 10.2337/dc07-0632.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.