Question

Diabetes- Which variable change causes the transition from prediabetic to diabetic?

Answer 1

Answer :

Prediabetes, typically defined as blood glucose levels above normal but below diabetes thresholds, is a risk state that defines a high chance of developing diabetes. Diagnostic criteria for prediabetes have changed over time and currently vary depending on the institution.
According to the World Health Organization (WHO), high risk for developing diabetes relates to two distinct states, impaired fasting glucose (IFG) defined as fasting plasma glucose (FPG) of 6.1–6.9 mmol/L (in the absence of impaired glucose tolerance – IGT) and IGT defined as postload plasma glucose of 7.8–11.0 mmol/L based on 2-h oral glucose tolerance test (OGTT) or a combination of both. The American Diabetes Association (ADA), although applying the same thresholds for IGT, uses a lower cut-off value for IFG (FPG 5.6–6.9 mmol/L) and has additionally introduced haemoglobin A1c levels of 5.7–6.4% as a new category of high diabetes risk.

The term prediabetes itself has been critised on the basis that many people with prediabetes do not progress to diabetes, the term may imply that no intervention is necessary as no disease is present, and diabetes risk does not necessarily differ between people with prediabetes and those with a combination of other diabetes risk factors. Indeed, the WHO used the term ‘Intermediate Hyperglycaemia’ and an International Expert Committee convened by the ADA the ‘High Risk State of Developing Diabetes’ rather than ‘prediabetes’.

The reproducibility of prediabetes (~50%) is lower than that for diabetes (>70%) and the alternative definitions based on IFG, IGT and A1c define overlapping prediabetic groups with single or combined abnormalities. Isolated IFG and isolated IGT may define persons with different pathophysiological abnormalities and their combination marks a more advanced disturbance of glycaemic homeostasis. In Caucasians, for example, the overlap between IFG and IGT can be as low as 25%.

Individual risk factors for diabetes (eg history of gestational diabetes, first degree relative with diabetes) or a combination of risk factors (eg metabolic syndrome) can also be used to define populations at-risk for diabetes but their predictive value is poorer than that of prediabetes. In addition, risk scores for incident diabetes based on a combination of non-invasive or blood-based risk factors are under development to identify individuals at high risk of developing diabetes.

Progression from prediabetes to diabetes

Around 5–10% of people with prediabetes become diabetic annually although conversion rate varies by population characteristics and the definition of prediabetes. In a meta-analysis of prospective studies published up to 2004, annualised incidence rates of diabetes for isolated IGT (4–6%) and isolated IFG (6–9%) were lower than those for IFG and IGT combined (15–19%). In more recent major studies, progression estimates have been similar: the annualised incidence was 11% in the Diabetes Prevention Program (DPP) Outcomes Study, 6% among participants with IFG in the US Multi-Ethnic Study of Atherosclerosis (MESA),16 9% among participants with IFG and 7% among those with an A1c 5.7–6.4% in a Japanese population-based study. Studies suggest that the risk of diabetes development on the basis of FPG and 2-h postload glucose is broadly similar to that posed by A1c.

According to an ADA expert panel, up to 70% of individuals with prediabetes will eventually develop diabetes. In a Chinese diabetes prevention trial, the 20-year cumulative incidence of diabetes was even higher (>90%) among controls with an IGT defined with repeated OGTTs. For comparison, women with gestational diabetes have been suggested to have a 20%–60% risk of developing diabetes 5 to 10 years after pregnancy. This large heterogeneity in the estimates is probably due to the variation in the criteria used to define gestational diabetes and type 2 diabetes in these studies. In a recent meta-analysis of studies, 13% of mothers with gestational diabetes developed diabetes after pregnancy compared to 1% of mothers without gestational diabetes.