The risk of each of the microvascular and macrovascular complications of type 2 diabetes and cataract extraction was strongly associated with hyperglycaemia as measured by updated mean haemoglobin A1c
. The incidence rates for any end point related to diabetes, adjusted for age, sex, ethnic group, and duration of diabetes, increased with each higher category of updated mean haemoglobin A1c
, with no evidence of a threshold and with a threefold increase over the range of updated mean haemoglobin A1c
of <6% (median 5.6%) to
10% (median 10.6%) (figs and ). The unadjusted and adjusted incidence rates are shown in table . Figure shows the adjusted incidence rates for myocardial infarction and microvascular end points. The increase in the incidence rate for microvascular end points was greater over the range of increasing glycaemia than was the increase in the incidence rate for myocardial infarction. Thus at near normal concentrations of updated mean haemoglobin A1c
the risk of myocardial infarction was twice to three times that of a microvascular end point, whereas in the highest category of haemoglobin A1c
10%) the risks were of the same order.
Figure 1 Incidence rate and 95% confidence intervals for any end point related to diabetes by category of updated mean haemoglobin A1c concentration, adjusted for age, sex, and ethnic group, expressed for white men aged 50-54 years at diagnosis and with (more ...)
Figure 2 Incidence rates and 95% confidence intervals for myocardial infarction and microvascular complications by category of updated mean haemoglobin A1c concentration, adjusted for age, sex, and ethnic group, expressed for white men aged 50-54 years (more ...)
Table 2 Incidence of complications in patients with type 2 diabetes by category of updated mean haemoglobin A1c concentration (%). Rates per 1000 person years' follow up adjusted in Poisson regression model to white men aged 50 to 54 years at diagnosis (more ...)
The estimated hazard ratios associated with different categories of updated mean haemoglobin A1c concentration, relative to the lowest category, are shown as log linear plots in figures and . Mortality related to diabetes and all cause mortality were both strongly associated with glycaemia (P<0.0001). The risk of each of the complications evaluated rose with increasing updated mean haemoglobin A1c concentration both before and after adjustment for baseline variables including age, sex, ethnic group, lipid concentrations, blood pressure, smoking, and albuminuria. The decrease in risk for each 1% reduction in updated mean haemoglobin A1c concentration is shown in table and figures and . The glycaemia associated reduction in risk for microvascular end points and for amputation or death from peripheral vascular disease was greater (by 37% and 43% per 1% reduction in haemoglobin A1c concentration, respectively, each P<0.0001) than it was for myocardial infarction, stroke, and heart failure (by 14% (P<0.0001), 12% (P=0.035), and 16% (P=0.021) per 1% haemoglobin A1c, respectively) (fig ). In models that included a variable for conventional control of blood glucose or intensive control with either sulphonylurea or insulin, updated mean haemoglobin A1c remained associated with all complications, although for stroke and heart failure, where the numbers of events were lower than in the previous analyses, these were no longer significant. In these models, treatment of blood glucose per se had no association with any complication beyond that of mean updated haemoglobin A1c.
Table 3 Observational analysis of relation between glycaemic exposure and complications of diabetes as estimated by decrease in risk for 1% reduction in haemoglobin A1c (HbA1c) concentration, measured at baseline and as updated mean, controlled for age (more ...)
There was no indication of a threshold for any complication below which risk no longer decreased nor a level above which risk no longer increased. The updated mean haemoglobin A1c showed steeper relations than did baseline haemoglobin A1c (table ), and when both glycaemic variables were included in a model for all complications of diabetes only updated mean haemoglobin A1c reached significance (P<0.0001).