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Objective: Cerebral microvascular disease associated with type 2 diabetes may exacerbate the effects of aging on cognitive function. A considerable homology exists between the retinal and cerebral microcirculations; a hypothesized association between diabetic retinopathy (DR) and cognitive decline was examined in older people with type 2 diabetes.Research Design and Methods: In the population-based Edinburgh Type 2 Diabetes Study, 1,046 men and women aged 60-75 years with type 2 diabetes underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. A general cognitive ability score (g) was generated by principal components analysis. The Mill-Hill Vocabulary Scale was used to estimate premorbid cognitive ability. DR was graded using a modification of the Early Treatment of Diabetic Retinopathy Scale.Results: After age and sex adjustment, a significant relationship was observed with increasing severity of DR (none, mild, and moderate to severe) for most cognitive measures. Participants with moderate-to-severe retinopathy had the worst g and the worst performances on the individual tests. There was a significant interaction between sex and retinopathy for g. In male subjects, the associations of retinopathy with g (and with tests of verbal fluency, mental flexibility, and processing speed but not memory and nonverbal reasoning) persisted (P < 0.05) when further adjusted for vocabulary (to estimate lifetime cognitive decline), depression, sociodemographic characteristics, cardiovascular risk factors, and macrovascular disease.Conclusions: DR was independently associated with estimated lifetime cognitive decline in older men with type 2 diabetes, supporting the hypothesis that cerebral microvascular disease may contribute to their observed accelerated age-related cognitive decline. A sex interaction with stronger findings in men requires further confirmation. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes.Research Design and Methods: We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C-reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry.Results: In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P Conclusions: Acute hypoglycemia may provoke upregulation and release of vasoactive substances in adults with and without type 1 diabetes. This may be a putative mechanism for hypoglycemia-induced vascular injury. [ABSTRACT FROM AUTHOR]

Objective: People with type 2 diabetes are at increased risk of cognitive impairment but the mechanism is uncertain. Elevated glucocorticoid levels in rodents and humans are associated with cognitive impairment. We aimed to determine whether fasting cortisol levels are associated with cognitive ability and estimated lifetime cognitive change in an elderly population with type 2 diabetes.Research Design and Methods: This was a cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes, living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study). Cognitive abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility were tested, and a general cognitive ability factor, g, was derived. Prior intelligence was estimated from vocabulary testing, and adjustment for scores on this test was used to estimate lifetime cognitive change. Relationships between fasting morning plasma cortisol levels and cognitive ability and estimated cognitive change were tested. Models were adjusted for potential confounding and/or mediating variables including metabolic and cardiovascular variables.Results: In age-adjusted analyses, higher fasting cortisol levels were not associated with current g or with performance in individual cognitive domains. However, higher fasting cortisol levels were associated with greater estimated cognitive decline in g and in tests of working memory and processing speed, independent of mood, education, metabolic variables, and cardiovascular disease (P < 0.05).Conclusions: High morning cortisol levels in elderly people with type 2 diabetes are associated with estimated age-related cognitive change. Strategies targeted at lowering cortisol action may be useful in ameliorating cognitive decline in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether circulating levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha are associated with cognitive ability and estimated lifetime cognitive decline in an elderly population with type 2 diabetes.Research Design and Methods: A cross-sectional study of 1,066 men and women aged 60-75 years with type 2 diabetes and living in Lothian, Scotland (the Edinburgh Type 2 Diabetes Study), was performed. Seven cognitive tests were used to measure abilities in memory, nonverbal reasoning, information processing speed, executive function, and mental flexibility. The results were used to derive a general intelligence factor (g). A vocabulary-based test was administered as an estimate of peak prior cognitive ability. Results on the cognitive tests were assessed for statistical association with inflammatory markers measured in a venous blood sample at the time of cognitive testing.Results: Higher IL-6 and TNF-alpha levels were associated with poorer age- and sex-adjusted scores on the majority of the individual cognitive tests. They were also associated with g using standardized regression coefficients -0.074 to -0.173 (P < 0.05). After adjusting for vocabulary, education level, cardiovascular dysfunction, duration of diabetes, and glycemic control, IL-6 remained associated with three of the cognitive tests and with g.Conclusions: In this representative population of people with type 2 diabetes, elevated circulating levels of inflammatory markers were associated with poorer cognitive ability. IL-6 levels were also associated with estimated lifetime cognitive decline. [ABSTRACT FROM AUTHOR]

Strict glycaemic control is strongly advocated in people with type 2 diabetes to prevent vascular disease. However, the outcomes of two large clinical trials have indicated the potential dangers of pursuing this policy in those at high risk of cardiovascular disease, with an excess of fatal vascular events being associated with a higher frequency of severe hypoglycaemia. Hypoglycaemia secondary to insulin and sulphonylurea therapy is often associated with serious morbidity; anecdotal evidence has long implicated hypoglycaemia as a potential cause of myocardial ischaemia or a cardiac arrhythmia. Hypoglycaemia provokes sympatho-adrenal activation and counterregulatory hormone secretion, which exert pronounced cardiovascular effects. Although well tolerated in healthy people, the superimposition of these profound physiological effects on a diseased coronary vasculature and a dysfunctional cardiac conductive system may induce serious or even fatal cardiovascular events. These risks should influence therapeutic targets and the approach to diabetes management in people with diabetes with established vascular disease in whom exposure to severe hypoglycaemia could be dangerous. [ABSTRACT FROM AUTHOR]

BACKGROUND: To examine the relationship between glycaemic control and hypoglycaemia in patients with type 2 diabetes treated with metformin (Met) and either insulin lispro mixtures, given twice or thrice daily (LM + Met), or insulin glargine, given once daily (G + Met). METHODS: Data from three randomized clinical trials were pooled to compare effects of LM + Met with G + Met. RESULTS: The LM + Met group achieved lower mean HbA(1c) (mean+/-SE, 7.2+/-0.1 vs. 7.7+/-0.1%, p<0.0001) and all meals combined post-prandial blood glucose (BG) (8.9+/-0.1 vs. 10.2+/-0.1 mmol/L, p<0.0001) compared with the G + Met group, but had higher fasting blood glucose (8.1+/-0.1 vs. 6.8+/-0.1 mmol/L, p<0.0001) and insulin requirement (0.7+/-0.01 vs. 0.6+/-0.01 U/kg, p<0.0001). Over the entire study period, daytime hypoglycaemia was higher for the LM + Met group (10.3 vs. 3.5 episodes/patient/year, p<0.0001) than for the G + Met group; however, nocturnal hypoglycaemia was lower (3.4 vs. 6.6 episodes/patient/year, p=0.003). At endpoint, daytime hypoglycaemia was higher for the LM + Met group (6.2 vs. 1.4 episodes/patient/year, p<0.0001); however, nocturnal hypoglycaemia was similar in both groups (1.9 vs. 3.0 episodes/patient/year). An inverse relationship was observed between all confirmed hypoglycaemia and HbA(1c) at endpoint; for every 1% reduction in HbA(1c), the increase (in slope) was 1.4 episodes/patient/year (p=0.04). Patients with confirmed hypoglycaemia had lower HbA(1c) than patients without hypoglycaemia (7.39 vs. 7.64%, respectively; decrement=0.26%, p=0.026). CONCLUSIONS: These studies demonstrated an inverse relationship between HbA(1c) and 24-h and daytime hypoglycaemia. Lispro insulin mixtures provided lower HbA(1c) and post-prandial blood glucose values than glargine, but caused more daytime hypoglycaemia. Frequency of nocturnal hypoglycaemia was similar and severe hypoglycaemia was rare with both insulin regimens. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Some aspects of memory performance are impaired during acute hypoglycaemia. The hippocampus is critical to formation of long-term memory, and may be particularly sensitive to hypoglycaemia. This study examined whether moderate hypoglycaemia occurring after learning would disrupt the consolidation process, and used functional magnetic resonance imaging (fMRI) to identify accompanying changes in brain activation. METHODS: Sixteen non-diabetic subjects each underwent two glucose clamp studies. During euglycaemia (4.5 mmol/L), subjects tried to memorize a series of words and a series of pictures of faces. Then, either hypoglycaemia (2.5 mmol/L) was induced for one hour, or euglycaemia was maintained. During subsequent uncontrolled euglycaemia, subjects' recognition of the word and face stimuli was tested, with simultaneous fMRI to measure brain activation during recognition. RESULTS: Face identification scores were 67.2% after euglycaemia and 66.9% after hypoglycaemia (p = 0.895). Word identification scores were 78.0 and 77.1% respectively (p = 0.701). Analysis of the fMRI identified two foci where activation was altered after hypoglycaemia compared with euglycaemia, but these were not in regions associated with memory, and were probably statistical artefacts. CONCLUSIONS: One hour of hypoglycaemia at 2.5 mmol/L induced 20-40 min after learning did not disrupt memory consolidation. fMRI did not show evidence of altered brain activation after hypoglycaemia. Consolidation may be relatively resistant to hypoglycaemia, or may have been complete before hypoglycaemia was induced. The study was powered to detect a large effect, and provides some reassurance that moderate hypoglycaemia does not cause major disruption of previously learned memories in people with insulin-treated diabetes. Copyright (c) 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

AIMS: To examine the effects of acute insulin-induced hypoglycaemia on different aspects of attention and on general non-verbal reasoning in people with Type 1 diabetes. METHODS: A hyperinsulinaemic glucose clamp was used to maintain euglycaemia (4.5 mmol/l) or induce hypoglycaemia (2.6 mmol/l) on separate occasions in 16 adults with Type 1 diabetes each of whom were studied on two occasions in a counterbalanced order. During each study condition, the subjects completed parallel tests of cognitive function assessed by the Test of Everyday Attention and the Raven's Progressive Matrices. RESULTS: Hypoglycaemia caused a significant deterioration in tests sensitive to visual and auditory selective attention. During hypoglycaemia, attentional flexibility deteriorated and speed of information processing was delayed. Sustained attention and intelligence scores were preserved during hypoglycaemia. CONCLUSIONS: In people with Type 1 diabetes, hypoglycaemia causes a significant deterioration in attentional abilities, while non-verbal reasoning is preserved. It is likely therefore that many complex cognitive tasks which involve attention will be impaired during moderate hypoglycaemia during everyday life. [ABSTRACT FROM AUTHOR]

AIMS: To ascertain the frequency and identify predictors of self-reported hypoglycaemia in Type 1 and insulin-treated Type 2 diabetes. METHODS: A random sample of 267 people with insulin-treated diabetes were recruited from a population-based diabetes register in Tayside, Scotland. Each subject prospectively recorded the number of mild and severe hypoglycaemic episodes experienced over a 1-month period. Ordinal logistic regression was performed to identify potential predictors of hypoglycaemia. RESULTS: Five hundred and seventy-two hypoglycaemic events were reported by 155 patients. The participants with Type 1 diabetes had a total of 336 hypoglycaemic events with a rate of 42.89 events per patient per year. Of these, nine were severe hypoglycaemic events, with a rate of 1.15 events per patient per year. Participants with insulin-treated Type 2 diabetes experienced a total of 236 hypoglycaemic events with a rate of 16.37 events per patient per year. Of these, five were severe hypoglycaemic events, which would be equivalent to 0.35 events per patient per year. Predictors of hypoglycaemia in Type 1 diabetes were a history of previous hypoglycaemia (P = 0.006) and co-prescribing of any oral drug (P = 0.048). In patients with insulin-treated Type 2 diabetes, a history of previous hypoglycaemia (P < 0.0001) and duration of insulin treatment (P = 0.014) were significant predictors. CONCLUSION: The incidence of self-reported severe hypoglycaemia in insulin-treated Type 2 diabetes is lower than in Type 1 diabetes but does occur more often than previously reported and with sufficient frequency to cause significant morbidity. Duration of insulin treatment is a key predictor of hypoglycaemia in insulin-treated Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Hypoglycaemia is a common and feared side-effect of insulin therapy. To avoid severe hypoglycaemia, an individual must recognise the warning symptoms at an early stage and take steps to correct falling blood glucose levels through appropriate self-treatment. The symptoms of hypoglycaemia are age-group specific and change with duration of diabetes. Unfortunately, awareness of hypoglycaemia is impaired in approximately 25% of adults with type 1 diabetes. Although associated with increasing duration of diabetes, this acquired syndrome can occur in people with strict glycaemic control when HbA[1c] is lowered towards the non-diabetic range. Recurrent exposure to a low blood glucose level modifies the glycaemic thresholds at which neuroendocrine and symptomatic responses are initiated. Other important risk factors for severe hypoglycaemia include sleep, ACE genotype, age, and duration of diabetes. The introduction of insulin analogues and new insulin regimens have helped to limit the frequency of severe hypoglycaemia, particularly at night. Behavioural training, such as the Blood Glucose Awareness Training programme, also can decrease the occurrence of severe hypoglycaemia. The ability to predict and anticipate the risk of developing hypoglycaemia in different situations (such as during physical activity and driving) and increased perception of the early onset of hypoglycaemia, assisted by frequent blood glucose monitoring, may help people with insulin-treated diabetes to avoid severe hypoglycaemia. [ABSTRACT FROM AUTHOR]

AIMS: Hypoglycaemia is considered to be less common in people with insulin-treated Type 2 diabetes than in Type 1 diabetes. A retrospective survey was made of 215 people with insulin-treated Type 2 diabetes to quantify the frequency and nature of hypoglycaemia experienced. METHODS: The frequencies of mild (self-treated) and severe (required assistance) hypoglycaemia during the preceding year were estimated retrospectively. The usual symptoms of hypoglycaemia and state of awareness of hypoglycaemia were scored using validated questionnaires and any history suggestive of impaired hypoglycaemia awareness was documented. RESULTS: In this cohort, 157 (73%) had experienced hypoglycaemia since commencing insulin, the frequency of which increased with duration of diabetes and of insulin therapy and was inversely related to current HbA1c (all P < 0.05). During the preceding year, 32 individuals (15%) had experienced severe hypoglycaemia, with an estimated incidence for the entire group of 0.28 episodes/patient/year. Principal components analysis revealed two underlying symptom groups (autonomic and neuroglycopenic), similar to those reported previously by young adults with Type 1 diabetes, but the total symptom score declined with advancing age. Of the 157 with a history of hypoglycaemia, the 13 (8%) individuals who gave a history of impaired awareness of hypoglycaemia had experienced a ninefold higher incidence of severe hypoglycaemia than those with normal awareness, and reported experiencing mainly neuroglycopenic symptoms. CONCLUSIONS: While the overall frequencies of mild and severe hypoglycaemia were lower in insulin-treated Type 2 diabetes than have been reported previously in Type 1 diabetes, the risk of hypoglycaemia was greater with increasing duration of diabetes and of insulin therapy. Although impaired awareness of hypoglycaemia was uncommon, it was associated with a higher incidence of severe hypoglycaemia. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence, predisposing factors, and costs of emergency treatment of severe hypoglycemia in people with type 1 and type 2 diabetes.Research Design and Methods: Over a 12-month period, routinely collected datasets were analyzed in a population of 367,051 people, including 8,655 people with diabetes, to measure the incidence of severe hypoglycemia that required emergency assistance from Ninewells Hospital and Medical School (NHS) personnel including those in primary care, ambulance services, hospital accident and emergency departments, and inpatient care. Associated costs with these episodes were calculated.Results: A total of 244 episodes of severe hypoglycemia were recorded in 160 patients, comprising 69 (7.1%) people with type 1 diabetes, 66 (7.3%) with type 2 diabetes treated with insulin, and 23 (0.8%) with type 2 diabetes treated with sulfonylurea tablets. Incidence rates were 11.5 and 11.8 events per 100 patient-years for type 1 and type 2 patients treated with insulin, respectively. Age, duration, and socioeconomic status were identified as risk factors for severe hypoglycemia. One in three cases were treated solely by the ambulance service with no other contact from health care professionals. The total estimated cost of emergency treatment of severe hypoglycemia was Conclusions: Hypoglycemia requiring emergency assistance from health service personnel is as common in people with type 2 diabetes treated with insulin as in people with type 1 diabetes. It is associated with considerable NHS resource use that has a significant economic and personal cost. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is associated with chronic hyperglycemia and exposure to intermittent severe hypoglycemia. The long-term cerebral effects of these consequences of diabetes are ill defined. In this study, the history of preceding severe hypoglycemia and the presence of background retinopathy were examined in relation to cognitive ability (neuropsychological test battery) and brain structure (magnetic resonance imaging) in a cross-sectional evaluation of 74 young people with type 1 diabetes. Participants differed by their severe hypoglycemia exposure and degree of diabetic retinopathy and none had previous neuropsychological pathology. Severe hypoglycemia did not influence cognitive ability or brain structure. Background diabetic retinopathy was associated with small focal white-matter hyperintensities in the basal ganglia (33.3 vs. 4.7%, after correction for age, P = 0.005) and significant cognitive disadvantage, affecting fluid intelligence (P = 0.008, Eta(2) = 0.14), information processing (P = 0.001, Eta(2) = 0.22), and attention and concentration ability (P = 0.03, Eta(2) = 0.09). In conclusion, recurrent exposure to severe hypoglycemia alone in young people with type 1 diabetes had no detrimental impact on brain structure or function over the duration of diabetes examined. Chronic hyperglycemia (inferred by the presence of background diabetic retinopathy) may affect brain structure and function. [ABSTRACT FROM AUTHOR]

Hypoglycaemia and its consequences are a significant risk for many people who have type 2 diabetes, yet it is often under-recognised, and may be avoidable. Severe hypoglycaemic events have an impact on mortality, morbidity and quality of life of many people with type 2 diabetes. With current clinical guidelines recommending strict glycaemic control, it is likely that the clinical risk of hypoglycaemia will increase, such that better recognition of the symptoms of hypoglycaemia is increasingly important in order to reduce the risk of progression to more severe episodes. This article outlines a series of structured questions which may be useful in eliciting an accurate account of the frequency and severity of hypoglycaemic events. [ABSTRACT FROM AUTHOR]

Aims: To determine the prognosis associated with severe hypoglycaemia (SH) and diabetic ketoacidosis (DKA) in adults presenting to a hospital emergency department (ED)., Methods: Medical records of adults with type 1 (T1D) and type 2 (T2D) diabetes who attended the ED with SH and DKA between 1 January 2019 and 30 June 2023, were reviewed for comorbidities, long-term survival, mortality and causes of death., Results: A total of 429 episodes of DKA occurred in 293 people and 643 episodes of SH in 515 people. DKA predominated in T1D (77.6%) and SH in T2D (54.3%). In T2D, 32.3% of DKA events were associated with sodium-glucose cotransporter-2 inhibitor (SGLT2-i) medication. In both SH and DKA, patients with T2D were older and had more comorbidities than T1D, particularly cardiorenal disease, heart failure, cognitive impairment and cancer (all p < 0.005). Compared with T1D, mortality was higher in T2D after SH (48.4% vs. 19.9%, p < 0.005) and after DKA (30.8% vs. 13.4%, p = 0.001) with shorter median times to fatal outcome (SH: 134 vs. 511 days; DKA: 43 vs. 266 days, both p < 0.005). Long-term survival was lower (p < 0.005) and mortality risk was higher in T2D after index presentation with SH (HR 3.43 [95% CI: 2.43-4.84], p < 0.005) and DKA (HR 3.00 [95% CI: 1.77-5.10], p < 0.005). Irrespective of diabetes type, most causes of death in SH and DKA were non-cardiovascular., Conclusions: SH and DKA events requiring hospital treatment herald a poor prognosis with greater mortality in T2D adults with multimorbidity. A significant number of DKA episodes in T2D occurred in people receiving SGLT2-i medication., (© 2024 Diabetes UK.)

Aims/hypothesis: Glycaemic control and clinical outcomes in diabetes are improved by continuous subcutaneous insulin infusion (CSII). Atmospheric pressure changes during flights may affect insulin delivery from pumps and cause unintended metabolic consequences, including hypoglycaemia, in people with type 1 diabetes. The present report evaluates both hypobaric flight simulation and real-world data in pilots using insulin pumps while flying., Methods: In the flight simulation part of this study, an in vitro study of insulin pumps was conducted in a hypobaric chamber, de-pressurised to 550 mmHg to mimic the atmospheric pressure changes in airliner cabins during commercial flights. Insulin delivery rates and bubble formation were recorded for standard flight protocol. Insulin infusion sets, without pumps, were tested in a simulated rapid decompression scenario. The real-world observational study was a 7.5-year retrospective cohort study in which pre- and in-flight self-monitored blood glucose (SMBG) values were monitored in pilots with insulin-treated diabetes. Commercial and private pilots granted a medical certificate to fly within the European Union Aviation Safety Agency approved protocol and receiving insulin either by pump or multiple daily injections (MDI) were included., Results: In the flight simulation study, full cartridges over-delivered 0.60 U of insulin during a 20 min ascent and under-delivered by 0.51 U during descent compared with ground-level performance. During emergency rapid decompression, 5.6 U of excess insulin was delivered. In the real-world study, seven pilots using CSII recorded 4656 SMBG values during 2345 h of flying across 1081 flights. Only 33 (0.7%) values were outside an acceptable safe range (5.0-15.0 mmol/l [90-270 mg/dl]). No clinically significant fall in the median SMBG concentration was observed after aircraft ascent and no in-flight SMBG values were within the hypoglycaemic range (<4.0 mmol/l [<72 mg/dl]). Compared with pilots receiving MDI therapy, pilots using CSII recorded more SMBG values within the acceptable range (99.3% vs 97.5%), fewer values in the low red range (0.02% vs 0.1%), fewer in-flight out-of-range values (0.2% vs 1.3%) and maintained stricter glycaemic control during flight., Conclusions/interpretation: Ambient pressure reduction during simulated flights results in bubble formation and expansion within insulin cartridges. This causes unintended delivery of small insulin doses independent of pre-determined delivery rates and represents the maximum amount of insulin that could be delivered and retracted. However, in vivo, pilots using CSII in-flight did not experience a fall in blood glucose or episodes of hypoglycaemia during these atmospheric pressure changes and the use of insulin pumps can be endorsed in view of their clinical benefits., (© 2024. The Author(s).)

Many people with diabetes in the U.S. will seek or currently hold a license to drive. For many, a driver's license is essential for everyday life. Considerable discussion has focused on whether, and the extent to which, diabetes may be a relevant factor in determining driver ability and eligibility for a license. This statement addresses such issues in relation to current scientific and medical evidence. A diagnosis of diabetes on its own is not sufficient to make judgments about an individual driver's ability or safety. This statement provides an overview of existing licensing rules for people with diabetes in the U.S., addresses the factors that affect driving ability, identifies general guidelines for assessing driver fitness and determining appropriately tailored licensing restrictions, and provides practical guidance for health care professionals regarding clinical interventions and education for people with diabetes., (© 2024 by the American Diabetes Association.)

Competing Interests: We declare no competing interests.