Risk of hypoglycaemia in types 1 and 2 diabetes: Effects of treatment modalities and their duration
Open accessAbstract
Aims/hypothesis We explored the epidemiology of hypoglycaemia in individuals with insulin-treated diabetes by testing the hypothesis that diabetes type and duration of insulin treatment influence the risk of hypoglycaemia.Materials and methods This was an observational study over 9-12 months in six UK secondary care diabetes centres. Altogether 383 patients were involved. Patients were divided into the following three treatment groups for type 2 diabetes: (1) sulfonylureas, (2) insulin for <2 years and (3) insulin for >5 years, and into two treatment groups for type 1 diabetes, namely <5 years disease duration and >15 years disease duration. Self-reported (mild and severe) and biochemical episodes (interstitial glucose <2.2 mmol/l using continuous glucose monitoring) were recorded.Results Mild hypoglycaemia in type 2 diabetic patients on insulin for <2 years was less frequent than in type 1 patients with <5 years disease duration (mean rate: 4 vs 36 episodes per subject-year, p < 0.001). In type 2 diabetic patients treated with sulfonylureas or insulin for <2 years, no differences were observed in the proportion experiencing severe hypoglycaemia (7 vs 7%, difference 0 [95% CI: -7 to 9%]), mild symptomatic (39 vs 51%, difference 12 [-3 to 25%]) or interstitial glucose <2.2 mol/l (22 vs 20%, difference 2 [-13 to 10%]). Severe hypoglycaemia rates were comparable in patients with type 2 diabetes on sulfonylureas or insulin < 2 years (0.1 and 0.2 episodes per subject-year) and far less frequent than in type 1 diabetes (<5 years group, 1.1; >15 years group, 3.2.episodes per subject-year).Conclusions/interpretation During early insulin use in type 2 diabetes, the frequency of hypoglycaemia is generally equivalent to that observed in patients treated with sulfonylureas and considerably lower than during the first 5 years of treatment in type 1 diabetes.
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Iatrogenic hypoglycemia is more frequent in patients with profound endogenous insulin deficiency-type 1 diabetes and advanced type 2 diabetes.
“Iatrogenic hypoglycemia is more frequent in patients with profound endogenous insulin deficiency—type 1 diabetes and advanced type 2 diabetes—and its incidence increases with the duration of diabetes (23).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
The Discussion (page unavailable) supports the main claim: hypoglycaemia risk rises as beta-cell function declines in type 2 diabetes, approaching the risk seen in type 1 diabetes. The cited sentence also says incidence increases with diabetes duration, but the paper links increased risk in type 2 diabetes to duration of insulin therapy and reports no increase in mild hypoglycaemia with type 1 diabetes duration. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe incidence of iatrogenic hypoglycemia increases with the duration of diabetes.
“Iatrogenic hypoglycemia is more frequent in patients with profound endogenous insulin deficiency—type 1 diabetes and advanced type 2 diabetes—and its incidence increases with the duration of diabetes (23).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
The Discussion reports that severe hypoglycaemia increases with longer type 1 diabetes duration, but says mild hypoglycaemia does not. For type 2 diabetes, it links rising risk to the duration of insulin therapy, not directly to the duration of diabetes. The unqualified claim therefore overstates the findings. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSevere hypoglycemia in patients with type 2 diabetes occurs at rates of 35 to 70 per 100 patient-years.
“Severe hypoglycemia in patients with type 2 diabetes has been shown to occur at rates of 35 (24) to 70 (23) per 100 patient-years.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
Table 2 (Discussion; page unavailable) reports 0.7 severe episodes per person-year—70 per 100 person-years—for patients with type 2 diabetes treated with insulin for more than five years. It does not report the claimed lower rate of 35 per 100; rates also vary by treatment and its duration, so the range is not supported as a general rate for type 2 diabetes. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIatrogenic hypoglycemia occurs about two to three times more frequently in type 1 diabetes than in type 2 diabetes.
“It is caused by treatment with a sulfonylurea, glinide, or insulin and occurs about two to three times more frequently in type 1 diabetes than in type 2 diabetes (23,24).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
The Self-reported episodes section (page not provided) reports more hypoglycaemia in some type 1 groups, but not a two- to threefold difference: mild episodes were 22 times more frequent in short-duration type 1 diabetes than in type 2 diabetes during early insulin use. The Discussion (page not provided) says rates in type 2 diabetes after more than five years of insulin use were similar to those in short-duration type 1 diabetes. The claimed ratio therefore does not hold across the treatment and duration groups studied. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIatrogenic hypoglycemia is caused by treatment with a sulfonylurea, glinide, or insulin.
“It is caused by treatment with a sulfonylurea, glinide, or insulin and occurs about two to three times more frequently in type 1 diabetes than in type 2 diabetes (23,24).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
The Introduction identifies hypoglycaemia as a side effect of insulin therapy, and the Discussion reports a risk of severe hypoglycaemia associated with sulfonylureas. The paper studies those two treatments but does not address glinides, so it does not support the full list of causes. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Occurrences of severe hypoglycemia and DKA (9.0 and 0.6 events per 100 person-years, respectively, in the safety cohort) observed during the study period are in line with other literature with estimates ranging from 7 to 130 and 4 to 8 events per 100 person-years, respectively, in insulin-requiring diabetes populations using MDI therapy.
“Occurrences of severe hypoglycemia and DKA (9.0 and 0.6 events per 100 person-years, respectively, in the safety cohort) observed during the study period are in line with other literature with estimates ranging from 7 to 130 and 4 to 8 events per 100 person-years, respectively, in insulin-requiring diabetes populations using MDI therapy (39-43).”
From Observed Glycemic and Psychosocial Benefits in the Prospective Bigfoot Unity Real World Study: A 6-Month Analysis (2025) · cites this paper as [39]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredEvent rates for severe hypoglycemia in patients with type 1 diabetes range from 115 to 320 per 100 patient-years.
“Event rates for severe hypoglycemia for patients with type 1 diabetes range from 115 (24) to 320 (23) per 100 patient-years.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
U500 regular insulin may improve glycemia in persons with severe insulin resistance (e.g., requiring more than 200 total units of insulin per day).
“U500 regular insulin (contains 500 units/mL of regular insulin) may improve glycemia in the therapy of persons with DM who have severe insulin resistance (eg, require >200 total units of insulin/day).1102–1105”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1104]
The Introduction and Discussion address hypoglycaemia risk by diabetes type and duration of insulin therapy, not U500 insulin as a treatment for severe insulin resistance. Searches for U500, 500 units/mL, and the >200-units-per-day threshold found no passage addressing whether U500 improves glycaemia. (LLM, conf=0.78)
Experimental — accuracy not yet measuredEvent rates for severe hypoglycemia for patients with type 1 diabetes range from 115 to 320 per 100 patient-years.
“Event rates for severe hypoglycemia for patients with type 1 diabetes range from 115 (24) to 320 (23) per 100 patient-years.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
Iatrogenic hypoglycemia occurs about two to three times more frequently in type 1 diabetes than in type 2 diabetes.
“It is caused by treatment with a sulfonylurea, glinide, or insulin and occurs about two to three times more frequently in type 1 diabetes than in type 2 diabetes (23,24).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
Iatrogenic hypoglycemia is caused by treatment with a sulfonylurea, glinide, or insulin.
“It is caused by treatment with a sulfonylurea, glinide, or insulin and occurs about two to three times more frequently in type 1 diabetes than in type 2 diabetes (23,24).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
Severe hypoglycemia in patients with type 2 diabetes occurs at rates of 35 to 70 per 100 patient-years.
“Severe hypoglycemia in patients with type 2 diabetes has been shown to occur at rates of 35 (24) to 70 (23) per 100 patient-years.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [23]
T2D now accounts for the majority of severe diabetes-related hypoglycemic events (those resulting in hospitalization) owing to disease prevalence.
“but owing to disease prevalence (∼20-fold that of T1D globally), T2D now accounts for the majority of severe diabetes-related hypoglycemic events (i.e., those resulting in hospitalization) ( Heller et al., 2007 ; Ratner, 2018 ).”
From Pharmacologic inhibition of somatostatin receptor 2 to restore glucagon counterregulation in diabetes (2024) · cites this paper as Heller et al., 2007
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- Authors
- UK Hypoglycaemia Study Group
- Corresponding author
- UK Hypoglycaemia Study Group
- Venue
- Diabetologia
- Published
- 2007-04-06
- Volume
- 50
- Issue
- 6
- Pages
- 1140-1147
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W4250647894
- Cited by
- 825
- References
- 26
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 28 · 2023: 36 · 2022: 35 · 2021: 49 · 2020: 46 · 2019: 50 · 2018: 67 · 2017: 64 · 2016: 61 · 2015: 80 · 2014: 71 · 2013: 71 · 2012: 49
- FWCI
- 17.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
- Keywords
- hypoglycemia, type 1 diabetes, type 2 diabetes, insulin-treated diabetes, sulfonylureas, disease duration, severe hypoglycemia, interstitial glucose, continuous glucose monitoring, hypoglycemia risk
- MeSH terms
- Analysis of Variance, Blood Glucose, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Risk Factors, Blood Glucose Self-Monitoring, Incidence, Monitoring, Ambulatory
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