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Evidence summaries

Glycaemic Control for Slowing the Progression of Microvascular Complications in Diabetes Mellitus

Intensive glycaemic control is effective in reducing the risk of microvascular complications in people with type 1 and type 2 diabetes. Level of evidence: "A"

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.

Tight glycaemic control compared with non-tight control for preventing diabetic kidney disease (DKD) and its progression

Outcome (follow up)Relative effect(95% CI)Assumed risk - Control- Non-tight controlCorresponding 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 100033 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 10002 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 100039 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 10002 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 100011 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 100016 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 10007 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).

Intensive glucose control versus conventional glucose control for microvascular complications type 1 diabetes

OutcomesRelative effect(95% CI)Assumed risk - ControlCorresponding risk - Intensive treatment (95% CI)No of participants(studies) Quality of evidence
Manifestation of retinopathyFollow-up: 5 - 6.5 yearsRR 0.27 (0.18 to 0.42)232 per 100063 per 1000(42 to 97)768 (2) High
Manifestation of nephropathyFollow-up: 3.5 - 6.5 yearsRR 0.56 (0.46 to 0.68)284 per 1000159 per 1000(131 to 193)1475 (3) Moderate
Manifestation of neuropathyFollow-up: 5 - 6.5 yearsRR 0.35 (0.23 to 0.53)139 per 100049 per 1000(32 to 74)1203 (3) High
Progression of retinopathyFollow-up: 5 - 6.5 yearsRR 0.61 (0.49 to 0.76)387 per 1000236 per 1000(190 to 294)764 (2) Moderate
Progression of nephropathyFollow-up: 5 - 6.5 yearsRR 0.79(0.37 t0 1.70)14 per 100011 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

    References

    • Fullerton B, Jeitler K, Seitz M et al. Intensive glucose control versus conventional glucose control for type 1 diabetes mellitus. Cochrane Database Syst Rev 2014;(2):CD009122. [PubMed]
    • Perais J, Agarwal R, Evans JR et al. Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy. Cochrane Database Syst Rev 2023;2(2):CD013775. [PubMed]
    • Agrawal L, Azad N, Bahn GD et al. Long-term follow-up of intensive glycaemic control on renal outcomes in the Veterans Affairs Diabetes Trial (VADT). Diabetologia 2018;61(2):295-299. [PubMed]
    • Zoungas S, Arima H, Gerstein HC et al. Effects of intensive glucose control on microvascular outcomes in patients with type 2 diabetes: a meta-analysis of individual participant data from randomised controlled trials. Lancet Diabetes Endocrinol 2017;5(6):431-437. [PubMed]
    • Ruospo M, Saglimbene VM, Palmer SC et al. Glucose targets for preventing diabetic kidney disease and its progression. Cochrane Database Syst Rev 2017;(6):CD010137. [PubMed]

Primary/Secondary Keywords