Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia

Veneman, Th.F.; Mitrakou, A.; Mokan, M.; Cryer, Philip E.; Gerich, John E.

doi:10.2337/diabetes.42.9.1233

Cited by 101 publications

(95 citation statements)

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“…In 1991, Heller and Cryer (9) demonstrated in nondiabetic human subjects that two 2-h episodes of hypoglycemia were sufficient to blunt subsequent neuroendocrine and symptomatic responses to hypoglycemia. Subsequent studies confirmed that antecedent hypoglycemia reduces neuroendocrine responses to hypoglycemia, both in nondiabetic subjects (9 -11) and in patients with diabetes (12)(13)(14). Lending further credence to antecedent hypoglycemia as a primary instigator of HAAF, intensive insulin therapy has been clearly associated with suppressed counterregulatory responses (7,8,23), while meticulous avoidance of hypoglycemia can restore symptom and hormonal responses to hypoglycemia within a matter of weeks (24 -26).…”

Section: Discussionmentioning

confidence: 92%

Antecedent Hypercortisolemia Is Not Primarily Responsible for Generating Hypoglycemia-Associated Autonomic Failure

et al. 2006

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Hypoglycemia-associated autonomic failure (HAAF) occurs commonly in patients with longstanding diabetes, placing affected patients at increased risk for severe hypoglycemia. Previous studies have suggested that hypoglycemia-induced hypercortisolemia may be responsible for blunting subsequent sympathoadrenal responses to hypoglycemia; however, this view remains highly controversial. In this work, we sought to better define the role of antecedent hypercortisolemia in generating HAAF, using two complimentary experimental models in nondiabetic human subjects: 1) antecedent hydrocortisone infusions (simulating physiologic cortisol responses to hypoglycemia) and 2) antecedent hypoglycemia, with and without concurrent blockade of endogenous cortisol production using oral metyrapone. Our results showed no effect of antecedent hypercortisolemia on epinephrine responses to subsequent hypoglycemia (area under the curve/time 280 ؎ 53 vs. 337 ؎ 57 pg/ml, P ‫؍‬ 0.16). Of particular importance, selective blockade of endogenous cortisol production during antecedent hypoglycemia had no effect on subsequent counterregulatory responses to hypoglycemia. Compared with epinephrine responses following antecedent euglycemia (area under the curve/time 312 ؎ 38 pg/ml), epinephrine responses were comparably blunted following antecedent hypoglycemia, regardless of whether concurrent metyrapone blockade was employed (198 ؎ 28 vs. 192 ؎ 28 pg/ml, P ‫؍‬ NS). Similar results were obtained for glucagon and ACTH levels. Considered together, these observations provide strong evidence that hypoglycemiainduced hypercortisolemia is not primarily responsible for the generation of HAAF. Diabetes 55

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Section: Discussionmentioning

confidence: 92%

Antecedent Hypercortisolemia Is Not Primarily Responsible for Generating Hypoglycemia-Associated Autonomic Failure

et al. 2006

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“…Episodes of nocturnal hypoglycemia range from asymptomatic to severe and are potentially fatal if untreated. In addition, even asymptomatic nocturnal hypoglycemia impairs defenses against subsequent hypoglycemia (29,30), i.e., it causes defective glucose counterregulation and hypoglycemia unawareness (1,11). Therefore, it is appropriate to separate hypoglycemic events into nocturnal and daytime episodes.…”

Section: B) How Should Hypoglycemia Be Reported?mentioning

confidence: 99%

Defining and Reporting Hypoglycemia in Diabetes

2005

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“…All but two nocturnal hypoglycemia episodes were asymptomatic. Asymptomatic nocturnal hypoglycemia is important because it may impair counter-regulatory responses and increase the risk of subsequent more prolonged and severe hypoglycemia (22), and it has also been implicated in the increased mortality rates in young adults with type 1 diabetes (23).…”

Section: Adverse Eventsmentioning

confidence: 99%

Randomized Cross-Over Trial of Insulin Glargine Plus Lispro or NPH Insulin Plus Regular Human Insulin in Adolescents With Type 1 Diabetes on Intensive Insulin Regimens

et al. 2003

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OBJECTIVE—To compare blood glucose control and incidence of nocturnal hypoglycemia in adolescents with type 1 diabetes on multiple injection regimens managed with either an insulin analog combination or NPH insulin plus regular human insulin. RESEARCH DESIGN AND METHODS—In a randomized cross-over study, 28 adolescents with type 1 diabetes on multiple injection therapy received either insulin glargine prebedtime plus lispro preprandially (LIS/GLAR) or NPH insulin prebedtime plus regular human insulin preprandially (R/NPH). During each 16-week treatment arm, subjects completed home blood glucose profiles, and at the end of each treatment arm, they were admitted for an overnight metabolic profile. A total of 25 subjects completed the study. RESULTS—Compared with R/NPH therapy, LIS/GLAR was associated with lower mean blood glucose levels (LIS/GLAR versus R/NPH): fasting (8.0 vs. 9.2 mmol/l, P < 0.0001), 2 h postbreakfast (8.1 vs. 10.7 mmol/l, P < 0.0005), prelunch (8.9 vs. 10.1 mmol/l, P < 0.01), and 2 h postlunch (8.0 vs. 9.5 mmol/l, P < 0.002). However, there was no difference in mean blood glucose levels before or after the evening meal. Incidence of nocturnal hypoglycemia on overnight profiles was 43% lower on LIS/GLAR compared with R/NPH therapy; however, there was no difference in rates of self-reported symptomatic hypoglycemia. Total insulin dose required to achieve target blood glucose control was lower on LIS/GLAR (1.16 IU/kg) compared with R/NPH therapy (1.26 IU/kg, P < 0.005), but there was no significant difference in HbA1c levels (LIS/GLAR versus R/NPH: 8.7 vs. 9.1%, P = 0.13). CONCLUSIONS—Combination therapy with insulin glargine plus lispro reduced the incidence of nocturnal hypoglycemia and was at least as effective as R/NPH insulin therapy in maintaining glycemic control in adolescents on multiple injection regimens.

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Induction of hypoglycemia unawareness by asymptomatic nocturnal hypoglycemia

Cited by 101 publications

References 0 publications

Antecedent Hypercortisolemia Is Not Primarily Responsible for Generating Hypoglycemia-Associated Autonomic Failure

Antecedent Hypercortisolemia Is Not Primarily Responsible for Generating Hypoglycemia-Associated Autonomic Failure

Defining and Reporting Hypoglycemia in Diabetes

Randomized Cross-Over Trial of Insulin Glargine Plus Lispro or NPH Insulin Plus Regular Human Insulin in Adolescents With Type 1 Diabetes on Intensive Insulin Regimens

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