Impaired Awareness of Hypoglycaemia in Insulin-treated Type 2 Diabetes Mellitus

Author(s): Mohammad J. Alkhatatbeh* , Nedaa A. Abdalqader , Mohammad A.Y. Alqudah .

Journal Name: Current Diabetes Reviews

Volume 15 , Issue 5 , 2019

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Background: Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia as an adverse effect of insulin therapy. Hypoglycemia has dangerous consequences that result from neuroglycopenia and hypersecretion of counter-regulatory hormones. Patients who recognize early symptoms of hypoglycemia can initiate self-treatment and rectify the situation. Impaired Awareness of Hypoglycemia (IAH) predisposes patients to severe hypoglycemia and unconsciousness.

Objective: To assess the prevalence of IAH, the intensity of hypoglycaemic symptoms, the frequency of severe hypoglycemia and factors associated with IAH in patients with insulin-treated T2DM.

Methods: This is a cross-sectional study that used Clarke's and Gold's surveys to assess IAH and Edinburgh survey to assess the intensity of hypoglycemic symptoms in patients with insulin-treated T2DM (n= 388). The frequency of hypoglycemia and other data were collected by self-reporting or from medical records.

Results: The prevalence (95% confidence interval) of IAH was 17.01% (13.27%-20.75%) as determined by Clarke’s method and 5.93% (3.58-8.28) by Gold’s method (Odds= 3.25, p-value<0.00001). Drowsiness, hunger, sweating, tiredness, trembling and weakness, were the most intense hypoglycaemic symptoms, and 6.19% of participants reported at least one episode of severe hypoglycaemia within the past year. Regardless of classification method used, IAH is not dependent on age, gender, duration of T2DM or duration of insulin therapy (p-values>0.05). Instead, IAH is positively associated with frequency of hypoglycaemia during the previous six months (p-value<0.05) and development of severe hypoglycaemia within the past year (p-value <0.05).

Conclusion: This study highlights large variability in IAH depending on the method used for assessment. Increased hypoglycaemia frequency may increase the prevalence of IAH and thus the development of severe hypoglycemia.

Keywords: Insulin, hypoglycaemic symptoms, impaired awareness, symptom intensity, severe hypoglycaemia, type 2 diabetes.

American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care 2009; 32(Suppl. 1): S62-7.
Stolar M. Glycemic control and complications in type 2 diabetes mellitus. Am J Med 2010; 123(3)(Suppl.): S3-S11.
Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Med 2017; 130(6S): S4-S17.
Polonsky WH, Henry RR. Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors. Patient Prefer Adherence 2016; 10: 1299-307.
McCall AL. Insulin therapy and hypoglycemia. Endocrinol Metab Clin North Am 2012; 41(1): 57-87.
Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the american diabetes association and the endocrine society. Diabetes Care 2013; 36(5): 1384-95.
International hypoglycaemia study group. glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: a joint position statement of the american diabetes association and the european association for the study of diabetes. Diabetes Care 2017; 40(1): 155-7.
Sprague JE, Arbeláez AM. Glucose counterregulatory responses to hypoglycemia. Pediatr Endocrinol Rev 2011; 9(1): 463-75.
Amin A, Lau L, Crawford S, Edwards A, Pacaud D. Prospective assessment of hypoglycemia symptoms in children and adults with type 1 diabetes. Canadian J Diab 2014; 38(4): 263-8.
Martin-Timon I, Del Canizo-Gomez FJ. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes 2015; 6(7): 912-26.
Ly TT, Gallego PH, Davis EA, Jones TW. Impaired awareness of hypoglycemia in a population-based sample of children and adolescents with type 1 diabetes. Diabetes Care 2009; 32(10): 1802-6.
Shafiee G, Mohajeri-Tehrani M, Pajouhi M, Larijani B. The importance of hypoglycemia in diabetic patients. J Diabetes Metab Disord 2012; 11: 17.
Cha S-A, Yun J-S, Lim T-S, Hwang S, Yim E-J, Song K-H, et al. Severe hypoglycemia and cardiovascular or all-cause mortality in patients with type 2 diabetes. Diabetes Metab J 2016; 40(3): 202-10.
Olsen SE, Bjorgaas MR, Asvold BO, et al. Impaired awareness of hypoglycemia in adults with type 1 diabetes is not associated with autonomic dysfunction or peripheral neuropathy. Diabetes Care 2016; 39(3): 426-33.
Hendrieckx C, Hagger V, Jenkins A, Skinner TC, Pouwer F, Speight J. Severe hypoglycemia, impaired awareness of hypoglycemia, and self-monitoring in adults with type 1 diabetes: Results from Diabetes MILES-Australia. J Diabetes Complications 2017; 31(3): 577-82.
Schouwenberg BJ, Coenen MJ, Paterson AD, et al. Genetic determinants of impaired awareness of hypoglycemia in type 1 diabetes. Pharmacogenet Genomics 2017; 27(9): 323-8.
Bednarik P, Moheet AA, Grohn H, et al. Type 1 diabetes and impaired awareness of hypoglycemia are associated with reduced brain gray matter volumes. Front Neurosci 2017; 11: 529.
Zhu L, Ang LC, Tan WB, et al. A study to evaluate the prevalence of impaired awareness of hypoglycaemia in adults with type 2 diabetes in outpatient clinic in a tertiary care centre in Singapore. Ther Adv Endocrinol Metab 2017; 8(5): 69-74.
Schopman JE, Geddes J, Frier BM. Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulin-treated type 2 diabetes. Diabetes Res Clin Pract 2010; 87(1): 64-8.
Henderson JN, Allen KV, Deary IJ, Frier BM. Hypoglycaemia in insulin-treated Type 2 diabetes: frequency, symptoms and impaired awareness. Diabet Med 2003; 20(12): 1016-21.
Deary IJ, Hepburn DA, MacLeod KM, Frier BM. Partitioning the symptoms of hypoglycaemia using multi-sample confirmatory factor analysis. Diabetologia 1993; 36(8): 771-7.
Clarke WL, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W. Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care 1995; 18(4): 517-22.
Gold AE, MacLeod KM, Frier BM. Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care 1994; 17(7): 697-703.
Graveling AJ, Noyes KJ, Allerhand MH, et al. Prevalence of impaired awareness of hypoglycemia and identification of predictive symptoms in children and adolescents with type 1 diabetes. Pediatr Diabetes 2014; 15(3): 206-13.

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Article Details

Year: 2019
Page: [407 - 413]
Pages: 7
DOI: 10.2174/1573399814666180806144937
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