Hypoglycemia in Type 2 Diabetes

The importance of strict glycemic control to limit the risk of diabetic vascular complications is indisputable, but many barriers obstruct its attainment. Hypoglycemia is recognized to be a major limitation in achieving good control in type 1 diabetes (1) but has been considered to be a minor problem of the treatment modalities used for type 2 diabetes (2). This may be a misperception based on inadequate information. The burden of covert hypoglycemia associated with oral antidiabetic agents may be underestimated, and with the increasing use of insulin to treat type 2 diabetes, the actual prevalence of hypoglycemia is likely to escalate. The frequency and pathophysiology of hypoglycemia in type 2 diabetes and the relationship to different therapies was reviewed by conducting a literature search using the bibliographic database PubMed to identify publications in English from 1984 until 2005 related to hypoglycemia associated with treatment of type 2 diabetes, and the bibliographies of relevant articles were scrutinized for additional citations. Search terms included “type 2 diabetes,” “NIDDM,” “non-insulin-dependent diabetes,” “hypoglycemia,” and “hypoglycaemia.” ### Normal physiological responses to hypoglycemia The human brain primarily uses glucose as its source of energy. Under normal conditions, the brain is unable to synthesize or store glucose and is exquisitely vulnerable to glucose deprivation. To protect the integrity of the brain, several physiological mechanisms have evolved to respond to and limit the effects of hypoglycemia (3–6). In humans, the initial response to a decline in blood glucose is suppression of endogenous insulin secretion followed by release of counterregulatory hormones, of which glucagon and epinephrine (adrenaline) are the most potent. When blood glucose falls in a nondiabetic adult, the secretion of counterregulatory hormones and the onset of cognitive, physiological, and symptomatic changes occur at reproducible blood glucose thresholds (4,7) within a defined hierarchy (5) (Fig. 1). Subjective recognition of …