Iatrogenic hypoglycemia and quality of life in patients with type 2 diabetes mellitus.

Hypoglycemia is a common side effect of treatment of diabetes and is the main limiting factor in achieving glycemic control in patients with type 1 and type 2 diabetes. It is defined as a glucose concentration ≤70 mg/dl (3.9 mmol/L) by a consensus group in the United States and accompanied by acute symptoms such as dizziness, sweating, tremors, and palpitations. In type 2 DM, hypoglycemia is more prevalent in patients treated with insulin and insulin secretagogues. The primary cause of hypoglycemia is due to intensification of therapy to achieve a lower HbA1C target. In the UKPDS, ACCORD, and ADVANCE studies, the rate of severe hypoglycemia was two to three times higher in the intensively treated patients compared to standard therapy group. The risk of hypoglycemia is greater in older patients, those with longer DM duration, kidney failure, and those with lesser insulin reserve. Dementia is another important risk factor for hypoglycemia, and conversely, recurrent hypoglycemia appears to increase the risk of dementia. Iatrogenic hypoglycemia represents a significant cause of morbidity and mortality in patients with type 1 and type 2 diabetes. In ADVANCE and ACCORD studies, severe hypoglycemia was associated with significant risk increases for cardiovascular events and mortality. A recent meta-analysis of prospective and retrospective clinical trials demonstrated that severe hypoglycemia doubled the risk of cardiovascular events. In addition, recurrent hypoglycemia can lead to long-term complications such as hypoglycemia associated autonomic neuropathy and cognitive dysfunction, leading to a cycle of recurrent hypoglycemia and hypoglycemia unawareness. There is a growing body of literature addressing the problem of fear of hypoglycemia, social anxiety and quality of life in young patients with type 1 diabetes, but few studies have addressed the relationship between hypoglycemia and quality of life in type 2 diabetes. These studies have suggested that hypoglycemia can impact on quality of life, productivity and increased worry for patients, poor medication adherence and increased healthcare costs. The cross-sectional study conducted in Spain by Jodar-Gimeno et al. adds and supports existing literature regarding decreased quality of life in patients with diabetes who experience hypoglycemia. They conducted quality of life measures using the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) and the Worry Subscale of the Hypoglycemic Fear Survey-II (HFS-II) in a large cohort of patients (n = 3812) with type 2 diabetes. They then compared the ADDQoL and HFS-II score between patients who experienced hypoglycemia to those who did not experience hypoglycemia in the 6 months prior to inclusion in the study. The study found that 45% of the patients with type 2 DM (n = 1711) experienced hypoglycemia in the 6 months prior to inclusion in the study. While the general quality of life measure did not differ between the groups, there was a significant difference in the specific questions in the ADDQoL measures, with patients with hypoglycemia having a worse quality of life than those who did not experience hypoglycemia. Additionally, patients with hypoglycemia also experienced more worry as assessed by HFS-II compared to patients who did not experience hypoglycemia and higher degree of worry was associated with a lower quality of life. The results of this study are similar to others that assessed quality of life in patients with type 2 diabetes and hypoglycemia. An interesting aspect of this study is that patients with hypoglycemia had more microvascular and macrovascular complications of diabetes. It brings up the question whether they had higher complications due to poor glycemic control from fear of hypoglycemia or whether increased complications, especially microvascular complications such as neuropathy made them more prone to hypoglycemia. It has been hypothesized that the increased worry accompanied by hypoglycemia may in turn have implications for