Hypoglycaemia induces a sustained pro-inflammatory response in people with type 1 diabetes and healthy controls

Aim: To determine the duration and the extension of the pro-inflammatory response to hypoglycaemia both in people with type 1 diabetes and healthy controls. Materials and Methods: Adults with type 1 diabetes (n = 47) and matched controls (n = 16) underwent a hyperinsulinaemic-euglycaemic hypoglycaemic (2.8 ± 0.1 mmoL/L [49.9 ± 2.3 mg/dL]) glucose clamp. During euglycaemia, hypoglycaemia, and 1, 3 and 7 days later, blood was drawn to determine immune cell phenotype, monocyte function and circulating inflammatory markers. Results: Hypoglycaemia increased lymphocyte and monocyte counts, which remained elevated for 1 week. The proportion of CD16+ monocytes increased and the proportion of CD14+ monocytes decreased. During hypoglycaemia, monocytes released more tumour necrosis factor-a and interleukin-1ß, and less interleukin-10, after ex vivo stimulation. Hypoglycaemia increased the levels of 19 circulating inflammatory proteins, including high sensitive C-reactive protein, most of which remained elevated for 1 week. The epinephrine peak in response to hypoglycaemia was positively correlated with immune cell number and phenotype, but not with the proteomic response. Conclusions: Overall, despite differences in prior exposure to hypoglycaemia, the pattern of the inflammatory responses to hypoglycaemia did not differ between people with type 1 diabetes and healthy controls. In conclusion, hypoglycaemia induces a range of pro-inflammatory responses that are sustained for at least 1 week in people with type 1 diabetes and healthy controls

Parkinson's disease: patient and general practitioner perspectives on the role of primary care

Background. Specialized Parkinson's disease (PD) care offers advantages to patients. However, specialized health care providers may be unaware of patients' personal context and comorbidity, leading to conflicting treatment regimens. Patients may benefit from a more holistic approach. Objective. To clarify the role community-dwelling PD patients see for general practitioners (GPs) in PD care and to clarify the role GPs see for themselves. Methods. Qualitative interview study with 16 community-dwelling PD patients and 12 GPs in the Netherlands, using a constant comparative approach to analysis. Results. Patients expressed a preference for self-management and autonomy in decisionmaking. GPs chose a limited, reactive position in early-stage PD care to stimulate patient autonomy. Moreover, GPs felt insufficiently competent to extend their role. Patients also felt GPs lack expert knowledge and skills; they focus on their neurologist for PD care. In addition, GPs observed patients might not realize what accessory role the GP could have, a role GPs described as essential in being aware of patient's well-being. Patients did not describe additional roles for the GP in more advanced disease, whereas GPs mentioned a shift towards a more proactive and extended role. Conclusion. Patients and GPs see a limited role for the GP in early-stage PD care because of patient autonomy and GP's lack of specific knowledge and skills. However, GPs should feel more confident of the added value of their generalist approach to care for patients with a complex chronic disorder as PD. If generalist and specialized care reinforce each other, PD patients benefit.Funding: the Dutch Parkinson’s Disease Association grant number 2012-V15 and the Health Insurers Innovation Foundation grant number 2687

Sustained pro-inflammatory effects of hypoglycemia in people with type 2 diabetes and in people without diabetes

Iatrogenic hypoglycaemia activates the immune system and is associated with an increased risk for atherosclerotic disease. We determined acute and long-term effects of insulin-induced hypoglycemia on inflammatory markers in humans with or without type 2 diabetes. Fifteen adults with type 2 diabetes and 16 matched controls (M/F 17/14, age 59.6±7.1 years, BMI 28.5±4.3 kg/m2) underwent a hyperinsulinemic-euglycemic (5.31±0.32 mmol/L) hypoglycemic (2.80±0.12 mmol/L) glucose clamp. Blood was drawn during euglycemia and hypoglycemia and 1, 3 and 7 days later, to determine circulating immune cell composition, function, and inflammatory proteins. In response to hypoglycemia, absolute numbers of circulating lymphocytes and monocytes significantly increased and remained elevated for one week. The proportion of CD16+ -monocytes increased, and the proportion of CD14+ -monocytes decreased, which sustained for a week in people without diabetes. During hypoglycemia, ex vivo stimulated, monocytes released more TNF-α and IL-1β, and less IL-10, particularly in people with diabetes. Hs-CRP and 25 circulating inflammatory proteins increased, remaining significantly elevated one week after hypoglycemia. While levels at euglycemia differed, responses to hypoglycemia were broadly similar in people with or without type 2 diabetes. We conclude that hypoglycemia induces a pro-inflammatory response at the cellular and protein level that is sustained for one week in people with type 2 diabetes and controls

Consistent effects of hypoglycemia on cognitive function in people with or without diabetes

Objective Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level Research design and methods Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 +/- 0.13 mmol/L [50.2 +/- 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP). Results For the whole group, hypoglycemia decreased the mean +/- SD proportion of correct answers on the PASAT by 8.4 +/- 12.8%, increased reaction time on the TAP Alertness task by 32.1 +/- 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 +/- 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA(1c). Conclusions IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemi

Additional file 1 of The impact of prior exposure to hypoglycaemia on the inflammatory response to a subsequent hypoglycaemic episode

Additional file 1. Supplement 1: in-and exclusions criteria

Consistent Effects of Hypoglycemia on Cognitive Function in People With or Without Diabetes.

OBJECTIVE: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level <3.0 mmol/L as "level 2 hypoglycemia." In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association. RESEARCH DESIGN AND METHODS: Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose clamp (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP). RESULTS: For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P < 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c. CONCLUSIONS: IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia <3.0 mmol/L (<54 mg/dL) as being clinically relevant for most people with diabetes.Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777460. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and T1D Exchange, JDRF, International Diabetes Federation (IDF), The Leona M. and Harry B. Helmsley Charitable Trust