A recent Article published in The Lancet suggests that the criteria for diagnosing diabetes mellitus could need reassessment. This conclusion comes from a study that looks at the connection between diabetes mellitus and a frequent diabetic complication called retinopathy.
Diabetes mellitus is a disorder due to an inability of pancreatic cells to produce enough insulin in order to prevent inappropriately high blood sugar (hyperglycemia). It is estimated to affect 380 million people by 2025. Diagnosis of the disorder, by both the World Health Organization (WHO) and the American Diabetes Association, is based on an individual’s “fasting plasma glucose” (FPG) concentration. The guideline for diagnosis is a 7·0 mmol/L or higher FPG concentration.
Retinopathy is a common complication associated with diabetes that is characterized by small blood vessel damage to the eye; it can also lead to blindness. In the 1990s, three studies of retinopathy indicated that the condition was unusual for patients with an FPG below 7·0 mmol/L, but that the prevalence increased substantially above that threshold. These three studies used either direct clinical ophthalmoscopic examination or one retinal photograph, not multiple field retinal photographs that are now considered the gold standard of clinical trials. In addition, the Diabetes Prevention Program has reported that many people have signs of retinopathy even when their FPG is below 7·0 mmol/L.
This most recent study – conducted by Professor Tien Wong, Center for Eye Research Australia, University of Melbourne, VIC, Australia, and colleagues – analyzed three more papers that used multiple field retinal photographs in order to define retinopathy. The three studies include:
- The Blue Mountains Eye Study (BMES), Australia, 3162 people
- The Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), Australia, 2182 people
- The Multi-Ethnic Study of Atherosclerosis (MESA), USA, 6079 people.
Wong and colleagues report that 9.6% to 15.8% of the general population had retinopathy, and there was no evidence of a clear and consistent FPG threshold for the presence or incidence of retinopathy across the populations. Further, the usual FPG cutoff of 7·0 mmol/L was too high to capture all retinopathy cases. More than 60% of cases were missed because the FPG levels were below the limit.
“We found no uniform FPG glycemic threshold for retinopathy across different populations and poor performance of current FPG cutoffs in separating individuals with and without retinopathy, largely due to the much higher prevalence of retinopathy at low FPG concentrations than previous studies reported,” write the authors.
Wong and colleagues conclude: “These findings could help unify the understanding of the risk of complications from diabetes, suggesting that both macrovascular (large vessel) and microvascular (small vessel) complications do not seem to respect a glycemic threshold. These findings further question the validity of the current WHO and American Diabetes Association approach of using retinopathy to derive FPG thresholds for diagnosing diabetes, and point to the need to revisit current diagnostic criteria for diabetes.”
Drs. Quresh Mohamed and Alison Evans, Cheltenham General Hospital, Cheltenham, UK, wrote in an accompanying editorial that although the current diagnostic criteria may be limited, the FPG threshold is able to distinguish a set of patients with a much greater risk of harm. They suggest a need for larger prospective studies that analyze diabetes and the complications that are associated with it.
“We perhaps should focus less on a single universal cut-off and instead target resources on the basis of standardized evidence-based individual risk scores in which measures of glycemia are combined with other risk factors. But what would we tell our patients when they asked if they had diabetes? We are probably best sticking with what we know until a better alternative diagnostic tool becomes available,” conclude Drs. Mohamed and Evans.
Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies
Tien Y. Wongm, Gerald Liew, Robyn J. Tapp, Prof Maria Inês Schmidt, Jie Jin Wang, Paul Mitchell, Ronald Klein, Barbara EK Klein, Paul Zimmet, and Jonathan Shaw
The Lancet (2008). 371:736-743
doi:10.1016/S0140-6736(08)60343-8
Written by: Peter M Crosta