If both parents have type 2 diabetes, should the living donation be allowed if oral glucose tolerance test is normal?
Thank you for your excellent question:
I have actually expanded your question into two parts:
1) What information does an oral glucose tolerance test provide compared to fasting glucose?
2) Can a current normal oral glucose tolerance test in the setting of a patient with other risk factors help refine the future risk of diabetes?
1) The determinants of elevated fasting glucose and 2-h plasma glucose in an oral glucose tolerance test (2-HPG) levels differ.
Raised hepatic glucose output and a defect in early insulin secretion are characteristic of the former, and peripheral insulin resistance is most characteristic of the latter.
Therefore, concordance between the categories of IFG and IGT is limited. About half or less of people with IFG have IGT, and even a lower proportion (20-30%) with IGT also have IFG. In the majority of studies, IGT is more prevalent than IFG, and there is a difference in phenotype and gender distribution between the two categories. IFG is substantially more common amongst men and IGT slightly more common amongst women. The prevalence of IFG tends to plateau in middle age whereas the prevalence of IGT rises into old age.
Both IFG and IGT are associated with an increased risk of developing diabetes, with the highest risk in people with combined IFG and IGT. Because IGT is commoner than IFG in most populations it is more sensitive (but slightly less specific) for identifying people who will develop diabetes. The OGTT is also less reproducible than the fasting glucose test.
In most studies, 60% of people who develop diabetes have either IGT or IFG 5 years or so before, with the other 40% having normal glucose tolerance at that time.
2) Although research protocols for estimating the future risk of diabetes have primarily depended upon identification of impaired glucose tolerance through a 2 hour oral glucose tolerance test, other clinical, historical and laboratory measures are known risk factors for diabetes. There are no studies to my knowledge that compare risk of diabetes in patients with risk factors (such as parental history) but current normal laboratory tests. Most studies predict risk of progression to diabetes in patients with impaired glucose tolerance ( Edelstein et al).
A recent study in the Annals of Internal Medicine (Khan et al) Compared two risk scores for predicting future diabetes in adults aged 45-64 years. The first risk score was based on clinical and historical criteria only (diabetes in mother, father, sex, smoking history, hypertension, Black race, waist circumference, height, pulse, weight), while the second score also included laboratory tests including fasting glucose, triglycerides, and uric acid. NOte both scores included maternal and paternal history of diabetes.
The risk scores had reasonable sensitivity and specificity for development of diabetes over the next 10 years ( AUC 0.71 and 0.79). These risk scores could be applied to your patient.
Once the risk in your patient is determined, it is important to note that numerous studies have shown that diabetes can be prevented by lifestyle modification and potentially by the use of medications (metformin).
Your final decision to move forward should consider the baseline risk in your donor and your assessment of whether your donor can implement lifestyle changes to modify this risk.
Edelstein SL, Knowler WC, Bain RP, Andres R, Barrett-Connor EL, Dowse
GK, et al. Predictors of progression from impaired glucose tolerance to NIDDM:
an analysis of six prospective studies. Diabetes. 1997;46:701-10.
Khan et al Ann Intern Med. 2009;150:741-751.