Technology to Reduce Hypoglycemia

Abstract

Hypoglycemia remains a major limiting factor toward the intensification of treatment for diabetes mellitus 1 and is a major cost to patients and to health care systems. 2 Hypoglycemia is often divided into mild or nonsevere hypoglycemia episodes (NSHE), where the person is able to selftreat, and severe hypoglycemia (SH), where external assistance is required. It is difficult to set a biochemical threshold for hypoglycemia, as the glucose threshold at which symptoms of hypoglycemia can be detected vary between individuals and even from day to day within the same person.3 The ADA workgroup on hypoglycemia offers some consensus guidelines, defining an alert value of ≤70 mg/dl, measured through self-monitored blood glucose (SMBG) or subcutaneous continuous glucose monitoring (CGM), as indicative of the potential for developing hypoglycemia. 4 All those treated with insulin secretagogues (sulphonylureas, glinides) and insulin therapy are at risk of hypoglycemia, and this risk is increased in the presence of endogenous insulin deficiency, longer duration of diabetes and longer duration of insulin therapy.5 Epidemiological data suggest that people with type 1 diabetes (T1D) with optimal glycemic control experience up to 2 mild episodes/week, with 20-30% experiencing episodes severe enough to require external help in any given year.6 A small proportion of these people, usually with impaired awareness of hypoglycemia, contribute to more than half of the incidence of SH, having recurrent disabling and sometimes life threatening events. 7CGM studies designed to study normative data suggest that while hypoglycemia is common in all insulin-treated people with diabetes, compared to subjects with type 2 diabetes (T2D), T1D subjects had twice as many hypoglycemic episodes per day, with more hours per day in the hypoglycemic range.8 However, although the incidence per patient of NSHE and SH is lower in T2D, due to the greater prevalence of T2D, the majority of episodes of SH occur in people with T2D. 9 In the US, rates of admissions for hypoglycemia have increased in recent years to 105 admissions per 100 000 person-years. 10 Antecedent hypoglycemia has been shown to blunt symptom and counter-regulatory hormonal responses to subsequent hypoglycemia.11 Over time, recurrent hypoglycemia eventually leads to a reduction in the ability to detect hypoglycemia and mount a hormonal response to it, known as impaired awareness of hypoglycemia (IAH) which can increase the risk of SH 6-fold. 12 In the T1D Exchange clinic registry, ≥ 1 SH events occurred in ~6% of over 9000 participants within 12 months, and was not associated with baseline glycated hemoglobin (HbA1c) levels. 13 Undoubtedly, SH has substantial clinical consequences on morbidity (both physical and psychological) and mortality. The more subtle effects of SH and hypoglycemia unawareness are often AbstractHypoglycemia is a major barrier toward achieving glycemic targets and is associated with significant morbidity (both psychological and physical) and mortality. This article re...

Decreasing Trends in Mean HbA1c Are Not Associated With Increasing Rates of Severe Hypoglycemia in Children: A Longitudinal Analysis of Two Contemporary Population-Based Pediatric Type 1 Diabetes Registries From Australia and Germany/Austria Between 1995 and 2016

“…The concurrent decreasing trends in HbA 1c and SH rates observed in this longitudinal study of two independent cohorts provide strong evidence that the relationship between HbA 1c and SH rates has changed in developed countries (19,21,23) where modern diabetes therapies and technology are being used to treat pediatric patients with type 1 diabetes by health professionals in well-developed pediatric diabetes care programs. Advances in diabetes therapies and technologies over the past decades including insulin analogs, pump therapy, continuous glucose monitoring, and patient/carer education, together with increasing clinical experience in the use of these diabetes management tools, are likely to have resulted in reduction in HbA 1c without an increase in SH rates (10,13,32,33). Importantly, reduced SH rates over time were observed in all HbA 1c groups, including the lowest HbA 1c group, in both of the cohorts analyzed in this study.…”

“…Over the past two decades, considerable advances have been made in diabetes therapies and technologies (10). In conjunction with these technological advances and newer insulins, changes in patient education over the past decades include the use of multidisciplinary teams, education of families and groups, the use of carbohydrate counting, and specific education on hypoglycemia awareness.…”

Characteristics of adults with type 1 diabetes and treatment-resistant problematic hypoglycaemia: a baseline analysis from the HARPdoc RCT

“…The HFS-II is a validated 33-item questionnaire to assess levels of fear around hypoglycaemia [24]. It has two subscales for behaviour (HFS-B, items 1-15) and worry (HFS-W, items [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Participants score each item from 0 ('never') to 4 ('almost always').…”

Nasal Glucagon Versus Injectable Glucagon for Severe Hypoglycemia: A Cost-Offset and Budget Impact Analysis

“…For SHE prevention, novel approaches have been explored in recent years. 37,38 Treatment for SHEs, however, has seen little progress despite the challenges associated with IG. 13,34,39 In the 1980s and 1990s, initial research was conducted on nasally administered glucagon formulations but none was brought to market.…”