The 505 incident diabetic participants contributed a total of 801 fasting measurements. The corresponding number for the 6033 controls was 10,989. The mean age did not differ between the groups. As expected, the incident cases were more likely to be men and non-Caucasian, and they had higher body mass index than the controls (). At baseline, they also had higher fasting and postload plasma glucose, fasting and postload insulin, and HOMA2-%B, as well as a lower HOMA2-%S (all P <0.05).
Fasting plasma glucose (, )
Among the controls there was a slight increase of fasting plasma glucose over time (mean ± S.E. 0.004±0.001 mmol/L/year) with levels of 5.26±0.008 mmol/L 13 years before and 5.31±0.010 mmol/L at the end of follow-up. For incident diabetes cases a linear trend from 13 years to 3 years before the diagnosis was apparent but with a steeper slope (slope difference between cases and controls 0.028±0.007 mmol/L/year) – the corresponding levels were 5.47±0.04 and 5.79±0.04 mmol/L. In the last 3 years the trajectory followed a quadratic curve reaching 7.40±0.04 mmol/L at the time of the diagnosis.
Table 2 Fixed effects for the multilevel models of change for fasting glucose, 2-hour postload glucose, homeostasis model assessment insulin sensitivity (HOMA2-%S) and HOMA β-cell function (HOMA2-%B) before the diagnosis of diabetes mellitus or the end (more ...)
2-hour postload glucose (, )
Among the controls, 2-hour postload glucose values increased from 5.11±0.024 to 5.77±0.098 mmol/L during the 13 years of follow-up with a slope of 0.051±0.007 mmol/L/year. The slopes were not significantly different (case * time term) between the incident diabetes group and the controls during 13 to 6 years before the end of follow up, but incident cases had a 0.99±0.09 mmol/L higher glucose value throughout this period.
From the last 6 years before diagnosis postload glucose levels of incident diabetes cases followed a cubic trajectory with a flatter part between 5 to 3 years before the diagnosis. There was an approximately 1.5 times larger difference of postload glucose values between incident cases and controls during this period than in the preceding period of 13 to 6 years before the diagnosis.
Among the incident diabetes cases, a fast elevation of glucose levels was evident from 2 years before to the diagnosis onward (from 7.60±0.15 to 11.90±0.13 mmol/L).
HOMA insulin sensitivity (, )
During 13 to 5 years before the end of follow-up, HOMA2-%S decreased linearly with the same slope of 1.11±0.30 % per year among the incident diabetes cases and controls. Those with incident diabetes had a 34.2±3.1% lower insulin sensitivity value during this period. In the last 5 years before the diagnosis, HOMA2-%S decreased with a steeper slope in the incident cases compared with the controls (difference in slopes per year 2.76±0.85%), reaching the level of 86.7±4.7% at the end of follow-up.
HOMA β-cell function (, )
The calculated insulin secretion (HOMA2-%B) was flat for both groups between 13 and 4 years before the end of follow up. However, the HOMA2-%B value of 85.0% (SE 1.5) among the incident diabetes cases was on the average 10.4±1.5% higher than that in the controls. During the last 4 years before diagnosis, HOMA2-%B values of the incident diabetes cases followed a negative quadratic trajectory with a steep increase to 92.6±2.5% between years 4 to 3 before diagnosis followed by a steep decrease to a value of 62.4±2.3%.
The final models for trajectories of fasting and postload glucose, HOMA2-%S and HOMA2-%B were largely supported in a number of sensitivity analyses: in an extended study population including also those with 5 to 8 hours of fasting (total n = 7148, sensitivity analysis 1); in a sub-cohort of participants with no missing data prior to diagnosis (cases) or phase 8 (controls)(n = 1332, sensitivity analysis 2); and when the timing of diabetes was set to the midpoint between date of the diagnosis and the preceding examination to approximate the onset of the disease (n = 6290, sensitivity analysis 3) (online Appendix Table 1). Adjustment for time-varying BMI attenuated the difference in insulin sensitivity between cases and controls, but it had little effect on the differences in trajectories between these groups (online Appendix Table 2).