Hypoglycemia

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Key points

  • Hypoglycemia is a frequent occurrence for many patients with type 1 or type 2 diabetes treated with insulin or insulin secretagogues and those with renal insufficiency.

  • Episodes of hypoglycemia have significant morbidity and mortality and are the main limiting factor for achieving near optimal glycemic control.

  • Impaired glucose counterregulation and hypoglycemia unawareness are the major risk factors for severe hypoglycemia.

  • Risk factors, including impaired glucose counterregulation and

General considerations

Normally, plasma glucose concentrations are maintained within a relatively narrow range throughout the day (usually between 55 and 165 mg/dL, ∼3.0 and 9.0 mM/L) despite wide fluctuations in the delivery (eg, meals) and removal (eg, exercise) of glucose from the circulation. This is accomplished by a tightly linked balance between glucose production and glucose utilization regulated by complex mechanisms.

Hypoglycemia is to be avoided to protect the brain and prevent cognitive dysfunction.

Epidemiology of hypoglycemia

The reported incidence of hypoglycemia varies considerably among studies. For the purpose of reporting hypoglycemia in clinical trials, the American Diabetes Association and the Endocrine Society have developed 5 categories, as outlined in Table 1.3 The incidence of one category, severe hypoglycemia, has been determined more precisely, as it is defined as that associated with unconsciousness or requiring external assistance. The complete detection of chemical hypoglycemia (commonly defined as a

Risk factors for hypoglycemia

Risk factors for hypoglycemia are summarized in Box 1. Conventional risk factors relate to absolute or relative insulin excess. These include insulin doses that are excessive or ill-timed, missed meals or snacks, lack of compensation for increased exercise, alcohol ingestion, or mistaken insulin administration. However, a thorough analysis of a large number of episodes of severe hypoglycemia in the DCCT has indicated that such conventional risk factors explained only a minority of the episodes17

Normal Hypoglycemia Counterregulation and Hypoglycemia Awareness

Glucose counterregulation refers to the sum of the body’s defense mechanisms that prevent hypoglycemia from occurring and that restore euglycemia. Hypoglycemia awareness refers to the symptomatic responses of hypoglycemia that alert the patient of declining blood glucose levels.

In healthy postabsorptive humans (ie, after an overnight fast), the sum of glucose release by liver and kidney nearly equals systemic glucose utilization so that plasma glucose concentrations remain relatively stable.

Manifestations of hypoglycemia

Manifestations of hypoglycemia are nonspecific and can sometimes be noted by observers rather than patients themselves. They can be categorized as neurogenic (mostly due to sympathetic neural activation) and neuroglycopenic (due to brain glucose deprivation) (Box 2). Neurogenic manifestations, also called autonomic or sympathoadrenal, precede neuroglycopenic symptoms and allow patients to recognize and self-treat hypoglycemia. Patients with hypoglycemia unawareness are likely to have

Complications of hypoglycemia

An episode of severe hypoglycemia can be detrimental or even fatal mostly due to its effects on the central nervous system. At plasma glucose concentration of approximately 55 mg/dL (∼3 mM/L), cognitive impairment and electroencephalogram changes are demonstrable. Decreases below 40 mg/dL (∼2.5 mM/L) result in sleepiness and gross behavioral (eg, combativeness) abnormalities. Further decreases can produce coma, and values less than 30 mg/dL (∼1.6 mM/L), if prolonged, can cause seizures,

Treatment

Treatment is aimed at restoring euglycemia, preventing recurrences, and, if possible, alleviating the underlying cause.

In an insulin-taking diabetic patient with mild hypoglycemia due to a skipped meal, 15 to 20 g of oral carbohydrate every 15 to 20 minutes until the blood glucose is above 80 mg/dL (4.5 mM/L) constitutes adequate treatment (Box 3).97, 98 Examples for oral carbohydrate source are presented in Box 4. In a patient with more severe hypoglycemia resulting in obtundation, in whom

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  • Cited by (34)

    • Gastrointestinal autonomic neuropathy in diabetes

      2020, Autonomic Neuroscience: Basic and Clinical
      Citation Excerpt :

      Hypoglycemia is appropriately feared by patients with diabetes, and is often the limiting factor in achieving optimal glycemic control using insulin or sulfonylureas (Frier, 2014). In health, a hierarchy of protective responses is triggered by falling blood glucose levels, including the ‘early’ (glucagon and catecholamines) and ‘late’ (cortisol and growth hormone) counter-regulatory hormone responses (Alsahli and Gerich, 2013). It is not widely appreciated that gastric emptying is accelerated markedly in response to insulin-induced hypoglycemia, allowing for more rapid intestinal absorption of ingested nutrients (Russo et al., 2005; Marathe et al., 2019).

    • Multiple predictively equivalent risk models for handling missing data at time of prediction: With an application in severe hypoglycemia risk prediction for type 2 diabetes

      2020, Journal of Biomedical Informatics
      Citation Excerpt :

      Many clinical risk factors for hypoglycemia have been identified. These include older age, diabetes duration, burden of co-morbidities, glycemic treatment intensification, current insulin treatment, duration of insulin treatment and use of other T2DM medications [37–42]. Risk models predicting short-term (2–12 months) [43–48] and long-term (5 years) [49] hypoglycemia have been developed.

    • Renal glucose metabolism in normal physiological conditions and in diabetes

      2017, Diabetes Research and Clinical Practice
      Citation Excerpt :

      In respiratory acidosis patients, an increase in net renal glucose release has been demonstrated to be inversely proportional to blood pH [65]. ( C) Glucose counterregulation in diabetes: Patients with type 1 diabetes mellitus (T1DM) and prolonged type 2 diabetes mellitus (T2DM) lose their glucagon response and become dependent on catecholamine responses [66]. When glucagon response is lost, catecholamines become the major counterregulatory hormonal factor by increasing renal glucose release during hypoglycemia [67].

    • Social vulnerability and hypoglycemia among patients with diabetes

      2017, Endocrinologia, Diabetes y Nutricion
      Citation Excerpt :

      In fact, low socioeconomic status confers a risk of hypoglycemia similar to that attributed to insulin use.11 The global frequency of hypoglycemia varies considerably among studies, being greater in patients with type 1 diabetes (T1D) than in patients with type 2 diabetes (T2D).12–14 In the Diabetes Control and Complications Trial (DCCT), patients in the intensive arm had a 65% incidence of severe hypoglycemia, compared with 35% in the conventional group.

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    Disclosures: Dr Alsahli has nothing to disclose.

    Funding Sources: Dr Gerich: University of Rochester Senior Faculty Associates Program.

    Conflict of Interest: Dr Gerich: Consultant: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Sanofi-Aventis, and Janssen Pharmaceuticals.

    Speakers' Bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Sanofi-Aventis, and Janssen Pharmaceuticals.

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