Restoration of Self-Awareness of Hypoglycemia in Adults With Long-Standing Type 1 Diabetes

Abstract

OBJECTIVEImpaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial.RESEARCH DESIGN AND METHODSEighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies.RESULTSAfter intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420–780] vs. 710 [460–1,260], P = 0.02; metanephrine, 2,412 [−3,026 to 7,279] vs. 5,180 [−771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation.CONCLUSIONSEven in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance.

Interventions That Restore Awareness of Hypoglycemia in Adults With Type 1 Diabetes: A Systematic Review and Meta-analysis

“…(59,60,63). In the adults from Ly et al (58), there was an equivalent reduction in SH incidence in SAP and in conventional CSII but greater improvement in HA status with SAP.…”

“…Of studies conducting hyperinsulinemichypoglycemic clamps, one showed an increase in plasma metanephrine responses to hypoglycemia (59), and two showed no significant differences in hormone responses (58,61).…”

Impaired Awareness of Hypoglycemia and Driving Mishaps in Patients with Type 1 Diabetes Mellitus: A Multi-center Survey in Japan

“…17 Leelarathna et al reported that IAH and counter regulatory responses may be improved by a clinical strategy aimed at hypoglycemia. 18 In Japan, we also developed a BGAT training site (http://bgat.jp/index. jsp) in 2010.…”

Recovery of Hypoglycemia Awareness in Long-standing Type 1 Diabetes: A Multicenter 2 × 2 Factorial Randomized Controlled Trial Comparing Insulin Pump With Multiple Daily Injections and Continuous With Conventional Glucose Self-monitoring (HypoCOMPaSS)

“…A retrospective case-note audit of RT with or without LGS in adults with IAH reported reduced SH without restoration of hypoglycemia awareness (15), and it has been suggested that RT offers the potential of replacing physiological awareness with technological awareness (29). In a hypoglycemic clamp substudy in 18 participants within the current trial, the glucose level at which hypoglycemia was recognized and catecholamine response were improved by study participation without significant differences detected between interventions (30).…”