A Cochrane review [Abstract] 3 included 59 studies with persons having type 1 or type 2 diabetes. Higher glycated haemoglobin (HbA1c) levels (adjusted OR ranged from 1.11 (95% confidence interval (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 |
Another Cochrane review [Abstract] 2 included 12 studies with a total of 2 230 adults and children with T1D. Under intensive glucose control, the risk of developing microvascular complications was reduced compared to conventional treatment for retinopathy, nephropathy, and neuropathy (table T2). Regarding the progression of these complications after manifestation, the effect was weaker (retinopathy) or possibly not existent (nephropathy) (table T2). Major macrovascular outcomes (stroke and myocardial infarction) occurred very rarely. A subgroup analysis according to the baseline HbA1c of participants in the trials (low quality evidence) suggests that the risk of hypoglycaemia is possibly only increased for patients who started with relatively low HbA1c values (< 9.0%). Several of the included studies also showed a greater weight gain under intensive glucose control, and the risk of ketoacidosis was only increased in studies using insulin pumps in the intensive treatment group (very low quality evidence).
| Outcomes | Relative effect(95% CI) | Assumed risk - Control | Corresponding risk - Intensive treatment (95% CI) | No of participants(studies) Quality of evidence |
|---|---|---|---|---|
| Manifestation of retinopathyFollow-up: 5 - 6.5 years | RR 0.27 (0.18 to 0.42) | 232 per 1000 | 63 per 1000(42 to 97) | 768 (2) High |
| Manifestation of nephropathyFollow-up: 3.5 - 6.5 years | RR 0.56 (0.46 to 0.68) | 284 per 1000 | 159 per 1000(131 to 193) | 1475 (3) Moderate |
| Manifestation of neuropathyFollow-up: 5 - 6.5 years | RR 0.35 (0.23 to 0.53) | 139 per 1000 | 49 per 1000(32 to 74) | 1203 (3) High |
| Progression of retinopathyFollow-up: 5 - 6.5 years | RR 0.61 (0.49 to 0.76) | 387 per 1000 | 236 per 1000(190 to 294) | 764 (2) Moderate |
| Progression of nephropathyFollow-up: 5 - 6.5 years | RR 0.79(0.37 t0 1.70) | 14 per 1000 | 11 per 1000 (5 to 24) | 179 (3) Very low |
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 (0.87, 0.76 to 1.00; p=0.04), but was not reduced for nerve events (0.98, 0.87 to 1.09; p=0.68).
An RCT 6 randomly assigned 1791 veterans with diabetes from 20 Veterans Affairs medical centres to receive either intensive or standard glucose control for a median of 5.6 years. Significantly more people with intensive treatment maintained an eGFR>60 (OR 1.34; 95% CI 1.05 to 1.71). This benefit was most evident in patients with moderate risk (RR 1.3) or high risk (RR 2.3) of chronic kidney disease at the beginning. There were no significant differences between the groups for average HbA1c, blood pressure or lipid levels
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