A meta-analysis 5 included 4 trials with a total of 27 049 participants. Compared with less intensive glucose control, more intensive glucose control resulted in an absolute difference of -0.90% (95% CI -1.22 to -0.58) in mean HbA1c at completion of follow-up. The relative risk was reduced by 20% for kidney events (hazard ratio 0.80, 95% CI 0.72 to 0.88; p<0.0001) and by 13% for eye events (HR 0.87, 0.76 to 1.00; p=0.04), but was not reduced for nerve events (HR 0.98, 0.87 to 1.09; p=0.68).
A Cochrane review [Abstract] 3 included 59 studies with persons having type 1 or type 2 diabetes. Higher HbA1c levels (adjusted OR ranged from 1.11 [95% CI 0.93 to 1.32] to 2.10 [95% CI 1.64 to 2.69]) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 [95% CI 1.29 to 1.48] to 12.40 [95% CI 5.31 to 28.98]) are independent risk factors for the development of proliferative diabetic retinopathy in people with T1D and T2D.
Another Cochrane review [Abstract] 4 included 11 studies with a total of 29 141 subjects with T1D or T2D. Treatment duration was 56.7 months on average (range 6 months to 10 years). Studies included people with a range of kidney function. Tight glycaemic control (HbA1c under 7%) compared with standard control made little or no difference to doubling of serum creatinine (SCr), all-cause mortality, cardiovascular mortality, or sudden death T1. Onset and progression of microalbuminuria was decreased in tight glycaemic control group T1. There was a trend towards decreased end-stage kidney disease (ESKD) and risk of non-fatal myocardial infarction.
| Outcome (follow up) | Relative effect(95% CI) | Assumed risk - Control- Non-tight control | Corresponding risk - Intervention - Tight control (95% CI) | No. of participants(studies) Confidence of evidence |
|---|---|---|---|---|
| Doubling serum creatinine(8.3 years) | RR 0.84 (0.64 to 1.11) | 39 per 1000 | 33 per 1000 (25 to 43.3) | 26 874 (4) Low |
| End-stage kidney disease(5.9 years) | RR 0.62 (0.34 to 1.12) | 3 per 1000 | 2 per 1000 (1.0 to 3.4) | 23 332 (4) Low |
| Onset microalbuminuria(5.4 years) | RR 0.85 (0.77 to 0.94) | 46 per 1000 | 39 per 1000 (35.4 to 43.2) | 19 933 (4) Moderate |
| Progression of microalbuminuria(5.8 years) | RR 0.59 (0.38 to 0.93) | 4 per 1000 | 2 per 1000 (1.5 to 3.7) | 13 266 (5) Moderate |
| Cardiovascular mortality(4.4 years) | RR 1.19 (0.73 to 1.92) | 9 per 1000 | 11 per 1000 (6.6 to 17.3) | 23 673 (6) Low |
| All-cause mortality(5.6 years) | RR 0.99 (0.86 to 1.13) | 16 per 1000 | 16 per 1000 (13.8 to 18.1) | 29 094 (9) Moderate |
| Non-fatal myocardial infarction(5.6 years) | RR 0.82 (0.67 to 0.99) | 8 per 1000 | 7 per 1000 (5.4 to 7.9) | 25 596 (5) Moderate |
In the UKDPS study 1 the incidence of diabetic complications was recorded in relation to mean of yearly HBA1c measurements. 3 642 patients were included in analyses of relative risk. The analyses were adjusted for age at diagnosis, sex, ethnic group, smoking, albuminuria, systolic blood pressure, HDL and LDL cholesterol, and triglycerides. Each 1% reduction in updated mean HbA1c was associated with reductions in risk of 21% for any end point related to diabetes (95% CI 17% to 24%), 21% for deaths related to diabetes (95% CI 15% to 27%), 14% for myocardial infarction (95% CI 8% to 21%), and 37% for microvascular complications (95% CI 33% to 41%). No threshold of risk was observed for any endpoint.
A systematic review and meta-analysis 2 included 10 studies with the total of 178 929 participants with diabetes (5 trials with DMT2, 4 with predominantly DMT2 and 1 trial with DMT1) and 14 176 incident congestive heart failure (CHF) cases. All studies except one showed an increased risk of CHF with higher HbA1c. The overall adjusted risk ratio (RR) for CHF was 1.15 (95% CI 1.10 to 1.21) for each percentage point higher HbA1c. There was substantial unexplained heterogeneity across the studies (I²=83). In 7 studies reporting RRs with more than one degree of adjustment, the association was minimally altered after adjustment for several cardiovascular risk factors.
Comment: The quality of evidence is upgraded by large magnitude of effect.
Primary/Secondary Keywords