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. 2018 Jan 1;103(1):105-114.
doi: 10.1210/jc.2017-01516.

Continuous Glucose Monitoring for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes

Michael R Rickels  1 , Amy J Peleckis  1 , Cornelia Dalton-Bakes  1 , Joseph R Naji  1 , Nina A Ran  1 , Huong-Lan Nguyen  1 , Shannon O'Brien  1 , Sanjian Chen  2 , Insup Lee  2 , Mark H Schutta  1
Affiliations

Continuous Glucose Monitoring for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes

Michael R Rickels et al. J Clin Endocrinol Metab. .

Abstract

Context: Patients with long-standing type 1 diabetes (T1D) are at increased risk for severe hypoglycemia because of defects in glucose counterregulation and recognition of hypoglycemia symptoms, in part mediated through exposure to hypoglycemia.

Objective: To determine whether implementation of real-time continuous glucose monitoring (CGM) as a strategy for hypoglycemia avoidance could improve glucose counterregulation in patients with long-standing T1D and hypoglycemia unawareness.

Design, setting, participants, and intervention: Eleven patients with T1D disease duration of ∼31 years were studied longitudinally in the Clinical & Translational Research Center of the University of Pennsylvania before and 6 and 18 months after initiation of CGM and were compared with 12 nondiabetic control participants.

Main outcome measure: Endogenous glucose production response derived from paired hyperinsulinemic stepped-hypoglycemic and euglycemic clamps with infusion of 6,6-2H2-glucose.

Results: In patients with T1D, hypoglycemia awareness (Clarke score) and severity (HYPO score and severe events) improved (P < 0.01 for all) without change in hemoglobin A1c (baseline, 7.2% ± 0.2%). In response to insulin-induced hypoglycemia, endogenous glucose production did not change from before to 6 months (0.42 ± 0.08 vs 0.54 ± 0.07 mg·kg-1·min-1) but improved after 18 months (0.84 ± 0.15 mg·kg-1·min-1; P < 0.05 vs before CGM), albeit remaining less than in controls (1.39 ± 0.11 mg·kg-1·min-1; P ≤ 0.01 vs all).

Conclusions: Real-time CGM can improve awareness and reduce the burden of problematic hypoglycemia in patients with long-standing T1D, but with only modest improvement in the endogenous glucose production response that is required to prevent or correct low blood glucose.

Trial registration: ClinicalTrials.gov NCT01474889.

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Figures

Figure 1.
Figure 1.
Clinical measures of average glycemic control, (A) HbA1c, hypoglycemia unawareness, (B) Clarke score, temporal glucose variability, (C) glycemic lability index, and (D) hypoglycemia severity (HYPO score), before and throughout intervention with implementation of real-time CGM. The dotted lines give the thresholds for (A) target glycemic control, (B) reduced awareness of hypoglycemia (17), (C and D) and the 90th percentile for glycemic lability and hypoglycemia severity derived from a population of 100 patients with T1D (18). The box plots represent the median, upper and lower quartiles, mean (□), and range (error bars).
Figure 2.
Figure 2.
(A) Plasma insulin and (B) glucose during the hyperinsulinemic hypoglycemic clamp in patients with T1D before (■) and at 6 months (●) and 18 months (▲) after implementation of real-time (RT) CGM (n = 11), and in nondiabetic controls (▼, n = 12). The shaded area represents the 95% confidence interval for data derived from the hyperinsulinemic euglycemic control experiments (n = 44).
Figure 3.
Figure 3.
Counterregulatory hormone [(A) glucagon, (B) epinephrine], (C) EGP, and (D) autonomic symptom responses during the hyperinsulinemic hypoglycemic clamp in patients with T1D before (■) and at 6 months (●) and 18 months (▲) after implementation of real-time (RT) CGM (n = 11), and in nondiabetic controls (▼, n = 12). The shaded area represents the 95% confidence interval for data derived from the hyperinsulinemic euglycemic control experiments (n = 44).
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References

    1. Cryer PE, Davis SN, Shamoon H. Hypoglycemia in diabetes. Diabetes Care. 2003;26(6):1902–1912. - PubMed
    1. Cryer PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2004;350(22):2272–2279. - PubMed
    1. Pedersen-Bjergaard U, Pramming S, Heller SR, Wallace TM, Rasmussen AK, Jørgensen HV, Matthews DR, Hougaard P, Thorsteinsson B. Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection. Diabetes Metab Res Rev. 2004;20(6):479–486. - PubMed
    1. Weinstock RS, Xing D, Maahs DM, Michels A, Rickels MR, Peters AL, Bergenstal RM, Harris B, Dubose SN, Miller KM, Beck RW; T1D Exchange Clinic Network . Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J Clin Endocrinol Metab. 2013;98(8):3411–3419. - PubMed
    1. McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012;35(9):1897–1901. - PMC - PubMed

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