期刊
DIABETES CARE
卷 36, 期 12, 页码 4063-4070出版社
AMER DIABETES ASSOC
DOI: 10.2337/dc13-1004
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资金
- Diabetes UK
- Cambridge National Institute for Health Research Biomedical Research Centre
- Medtronic
- Sanofi Diabetes
- Lilly
- MSD
- Novo Nordisk
- Roche Diagnostics Australia
- Roche
- Abbott Diabetes Care
- Animas
- Eli Lilly
- LifeScan
- Sanofi
- Diabetes UK [07/0003556] Funding Source: researchfish
- Medical Research Council [G0600717, MC_UU_12012/5/B, G0600717B] Funding Source: researchfish
- National Institute for Health Research [ACF-2013-24-004] Funding Source: researchfish
- MRC [G0600717] Funding Source: UKRI
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, HbA(1c) 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 x 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.
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