Epidemiology and risk factors of hypoglycaemia in type 2 DM

The incidence of hypoglycaemia in type 2 diabetes is largely dependent on the therapy that patients are using. Patients that are treated with a diet or with the oral agent metformin only may not experience hypoglycaemia at all. Patients that are treated with sulfonylurea derivatives or basal insulin have some risk of hypoglycaemia, but this is much smaller than the risk of hypoglycaemia in patients with type 1 diabetes. Intensive glucose control has been shown to raise the risk for severe hypoglycaemia. When type 2 diabetes patients are fully insulin dependent their risk of hypoglycaemia may approach that of patients with type 1 diabetes.

Type 2 diabetes

Incidence of hypoglycaemia

Sulphonylurea derivatives A prospective British study investigated self-reported hypoglycaemia in patients with type 2 diabetes with an average HbA1c of 7.5% (58 mmol/mol)[1]. In this study subjects were asked to record episodes of hypoglycaemia if plasma glucose was 3.0 mmol/L over an average period of approximately nine months. Of the 103 sulfonylurea-treated patients, 39% experienced at least one episode of mild hypoglycaemia, for an average number of 1.92 episodes of mild hypoglycaemia per patient per year. Severe hypoglyacemia which required the help of a third party was estimated at 0.1 episodes per patient per year and affected 7%. In another British study, self-reported mild hypoglycaemia was reported by 17% of 922 sulfonylurea-treated patients. Severe hypoglycaemia which required medical assistance affected only 0.8% of the trial participants and the average number of severe hypoglycaemic episodes per patient per year was 0.009 [2].

Basal and premixed insulin Patients with type 2 diabetes on basal insulin treatment with concomitant oral therapy (all kinds) experience approximately 0.01-0.1 episodes of mild hypoglycaemia per patient year. The incidence of severe hypoglycaemia is approximately 0.01 episodes per patient per year. A recent major study showed that 57% of people on insulin glargine treatment (often in combination with an oral agent) experienced at least one episode of mild hypoglycaemia over a 6-year period[3].

Intensive insulin therapy Two large prospective studies from the UK have examined hypoglycaemia in insulin-treated T2DM, reporting incidences ranging from 4 to 16 episodes of mild hypoglycaemia per patient per year. The estimated incidence of severe hypoglycaemia in type 2 diabetes patient treated with an intensive insulin regimen ranges from 0.1 to 0.7 episodes per patient per year [4][5].

Other agents Monotherapy with metformin, dipeptidyl peptidase 4 inhibitors or glucagon like peptide-1 agonists rarely cause mild or severe hypoglycaemia. [6]

Risk factors for hypoglycaemia

Hypoglycemia in patients with type 2 diabetes is iatrogenic, and most frequently the consequence of the use of sulfonylurea derivatives or insulin therapy. There are some major factors that may increase the risk of hypoglycaemia:

  • wrong dose of glucose lowering drug
  • decreased intake of carbohydrates
  • increased insulin sensitivity, for instance after exercise or after weight loss
  • decreased endogenous glucose production, e.g. alcohol
  • impaired drug clearance, e.g. renal impairment

Elderly may have an increased risk of hypoglycaemia, especially when they have mental disabilities such as dementia. These patients are more likely to forget a meal or to make medication errors. Furthermore symptoms of hypoglycaemia may change with older age when general symptoms such as malaise become less pronounced and neuroglycopenic symptoms such as unsteadiness, poor co-ordination and double vision may become more prominent [7]. It is likely that these neuroglycopenic symptoms increase the risk for hypoglycaemia related falls. A recent meta-analysis of randomised trials showed that intensive glycaemic control increases the risk of severe hypoglycaemia with 30%[8]. Other risk factors include duration of insulin therapy, loss of residual insulin secretion and a defective counterregulation[9][10]. When insulin deficient patients with type 2 diabetes are compared with type 1 diabetes patients with a similar duration of insulin treatment, their risk of severe hypoglycaemia approaches the risk of those with type 1 diabetes[11]. Impaired awareness of hypoglycaemia increases the risk of severe hypoglycaemia manifold (6-9 times), but it is only present in 10 % of the insulin-treated type 2 diabetes patients [12].

References

  1. ^ UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 effects of treatment modalities and their duration, Diabetologia 50 (2007) 1140–1147.

  2. ^ UK prospective diabetes study 16. Overview of 6 years' therapy of type II a progressive disease. Diabetes 1249-1258, 1995

  3. ^ ORIGIN Trial Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 319-328, 2012

  4. ^ UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 effects of treatment modalities and their duration. Diabetologia 1140-1147, 2007

  5. ^ L.A. Donnelly, A.D. Morris, B.M. Frier, J.D. Ellis, P.T. Donnan, R. Durrant, et al.,for the DARTS/MEMO Collaboration, Frequency and predictors of hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes: a population-based study, Diabet. Med. 22 (2005) 749–755.

  6. ^ Richter B et al.: Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2008 Apr 16;(2).

  7. ^ Jaap AJ: Perceived symptoms of hypoglycaemia in elderly type 2 diabetic patients treated with insulin. Diabet Med. 1998 May;15(5):398-401.

  8. ^ Hemmingsen B et al.: Intensive glycaemic control for patients with type 2 diabetes: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ. 2011

  9. ^ Henderson JN et al.: Hypoglycaemia in insulin-treated Type 2 diabetes: frequency, symptoms and impaired awareness. Diabet Med. 2003 Dec;20(12):1016-21.

  10. ^ Segel SA, Paramore DS, Cryer PE. Hypoglycemia-associated autonomic failure in advanced type 2 diabetes. Diabetes. 2002 Mar;51(3):724-33.

  11. ^ Hepburn DA et al.: Frequency and symptoms of hypoglycaemia experienced by patients with type 2 diabetes treated with insulin. Diabet Med. 1993 Apr;10(3):231-7.

  12. ^ Schopman J.E., Geddes J., Frier B.M. Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulin-treated type 2 diabetes. Diabetes Res Clin Pract 2010; 87:64-68.

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