Association of glycaemic control and complications of type 2 diabetes

A meta-analysis «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 c»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 «Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy»1 «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»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 «Glucose targets for preventing diabetic kidney disease and its progression»2 «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. »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 « Tight glycaemic control compared with non-tight control for preventing diabetic kidney disease (DKD) and its progression»1. Onset and progression of microalbuminuria was decreased in tight glycaemic control group « Tight glycaemic control compared with non-tight control for preventing diabetic kidney disease (DKD) and its progression»1. There was a trend towards decreased end-stage kidney disease (ESKD) and risk of non-fatal myocardial infarction.

In the UKDPS study «Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 3»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 «Erqou S, Lee CT, Suffoletto M et al. Association between glycated haemoglobin and the risk of congestive heart failure in diabetes mellitus: systematic review and meta-analysis. Eur J Heart Fail 2013;»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.

A Comparative Effectiveness Study (GRADE) «Wexler DJ, Garvey WT, Ghosh A, et al. Weight Gain Was Associated With Worsening Glycemia and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes Independent of Diabetes Medication in t»6 randomized trial comparing the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D included 4980 participants. Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide, -1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride. Thereafter, weight decreased in all groups. Weight gain within the first 6 months was associated with increased risk of HbA1c >7.5%, with modest differences by treatment, and with subsequent CVD (HR 1.03, 95% CI 1.005 to 1.06). Weight gain at 1 year was associated with increased risk of HbA1c >7.5% (HR 1.05, 95% CI 1.04 to 1.07) and kidney disease (HR 1.03, 95% CI 1.01 to 1.06). Baseline weight, but not weight gain, was associated with new-onset neuropathy.

Comment: The quality of evidence is upgraded by large magnitude of effect.