The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study

Abstract

Objectives To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A1C) achieved during therapy.Design Post hoc epidemiological analysis of a double 2×2 factorial, randomised, controlled trial.Setting Diabetes clinics, research clinics, and primary care clinics.Participants 10 209 of the 10 251 participants enrolled in the ACCORD study with type 2 diabetes, a haemoglobin A1C concentration of 7.5% or more during screening, and aged 40-79 years with established cardiovascular disease or 55-79 years with evidence of significant atherosclerosis, albuminuria, left ventricular hypertrophy, or two or more additional risk factors for cardiovascular disease (dyslipidaemia, hypertension, current smoker, or obese).Interventions Intensive (haemoglobin A1C <6.0%) or standard (haemoglobin A1C 7.0-7.9%) glucose control.Main outcome measures Severe hypoglycaemia was defined as episodes of “low blood glucose” requiring the assistance of another person and documentation of either a plasma glucose less than 2.8 mmol/l (<50 mg/dl) or symptoms that promptly resolved with oral carbohydrate, intravenous glucose, or glucagon. Results The annual incidence of hypoglycaemia was 3.14% in the intensive treatment group and 1.03% in the standard glycaemia group. We found significantly increased risks for hypoglycaemia among women (P=0.0300), African-Americans (P<0.0001 compared with non-Hispanic whites), those with less than a high school education (P<0.0500 compared with college graduates), aged participants (P<0.0001 per 1 year increase), and those who used insulin at trial entry (P<0.0001). For every 1% unit decline in the haemoglobin A1C concentration from baseline to 4 month visit, there was a 28% (95% CI 19% to 37%) and 14% (4% to 23%) reduced risk of hypoglycaemia requiring medical assistance in the standard and intensive groups, respectively. In both treatment groups, the risk of hypoglycaemia requiring medical assistance increased with each 1% unit increment in the average updated haemoglobin A1C concentration (standard arm: hazard ratio 1.76, 95% CI 1.50 to 2.06; intensive arm: hazard ratio 1.15, 95% CI 1.02 to 1.21).Conclusions A greater drop in haemoglobin A1C concentration from baseline to the 4 month visit was not associated with an increased risk for hypoglycaemia. Patients with poorer glycaemic control had a greater risk of hypoglycaemia, irrespective of treatment group. Identification of baseline subgroups with increased risk for severe hypoglycaemia can provide guidance to clinicians attempting to modify patient therapy on the basis of individual risk.Trial registration ClinicalTrials.gov number NCT00000620.

Predictors of Nonsevere and Severe Hypoglycemia During Glucose-Lowering Treatment With Insulin Glargine or Standard Drugs in the ORIGIN Trial

“…In contrast, the independent determinants of severe hypoglycemia were older age, limited education, hypertension, renal insufficiency, and mild cognitive impairment. These observations are also consistent with those of other reports (5,(13)(14)(15)(16)(17). Stated in clinically relevant terms, these analyses suggest that an individual with a BMI of 25 kg/m 2 would be ;30% more likely to have nonsevere hypoglycemia than one with a BMI of 35 kg/m 2 , but with no difference in the risk of severe hypoglycemia.…”

Severe Hypoglycemia Is Associated With Antidiabetic Oral Treatment Compared With Insulin Analogs in Nursing Home Patients With Type 2 Diabetes and Dementia: Results From the DIMORA Study

“…9 An unexpected finding was that patients with dementia showed significantly higher A1c levels compared with those who did not experience severe hypoglycemia. Indeed, the literature has shown that lower A1c levels are generally associated with severe hypoglycemia 22,23 ; however, specific information on A1c levels in patients with dementia experiencing severe hypoglycemia are scare. A previous report in a large longitudinal study of older patients with type 2 diabetes also found significantly higher A1c levels in those who had experienced a severe hypoglycemic event compared with those who did not.…”

Trends in hospital admissions for hypoglycaemia in England: a retrospective, observational study

“…However, an epidemiological analysis of the ACCORD trial suggests that the risk of hypoglycaemia resulting in emergency medical care or admission to hospital is progressively higher in type 2 diabetes participants with lower baseline HbA1c when comparing intensive vs standard glucose-lowering treatments (around 2-times for values ≥8.5%; 3-times for values between 7.5-8.4%; and 7-times for values <7.5%). 33 It is noteworthy that the individualised identification of HbA1c targets is just one of a number of approaches to the problem of hypoglycaemia. 10 In observational studies, structured diabetes education reduce the burden of hypoglycaemia; 10 yet, attendance at structured education programs remains very low (5.3%) and further effort should be put in place to identify and address local barriers.…”