Insulin-Associated Weight Gain in Type 2 Diabetes Is Associated With Increases in Sedentary Behavior.

Contains fulltext : 177371.pdf (publisher's version ) (Closed access)01 september 201

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

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

BACKGROUND: Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans.METHODS: Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP.RESULTS: In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16+-monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1β, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia.CONCLUSION: Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia. Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019).</p

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

BACKGROUND: Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans.METHODS: Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP.RESULTS: In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16+-monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1β, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia.CONCLUSION: Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia. Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019).</p

Антицитрулінові антитіла в діагностиці артритів у дітей

Віходячи з проведеного дослідження, описаного в роботі, можна дійти висновку, що серед дітей із різними формами артритів тільки 4,8% пацієнтів були серопозитивними за РФ, та 23,8% дітей – за рівнем АЦЦП. Прогнастичне значення підвищеного рівня АЦЦП у дітей із РеА полягає в високій вірогідності розвитку ЮРА, що обумовлює більш ретельне їх спостереження із застосуванням індивідуальних схем профілактичного лікування. При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/1128

Counterregulatory hormone and symptom responses to hypoglycaemia in people with type 1 diabetes, insulin-treated type 2 diabetes or without diabetes:the Hypo-RESOLVE hypoglycaemic clamp study

Aim: The sympathetic nervous and hormonal counterregulatory responses to hypoglycaemia differ between people with type 1 and type 2 diabetes and may change along the course of diabetes, but have not been directly compared. We aimed to compare counterregulatory hormone and symptom responses to hypoglycaemia between people with type 1 diabetes, insulin-treated type 2 diabetes and controls without diabetes, using a standardised hyperinsulinaemic-hypoglycaemic clamp. Materials: We included 47 people with type 1 diabetes, 15 with insulin-treated type 2 diabetes, and 32 controls without diabetes. Controls were matched according to age and sex to the people with type 1 diabetes or with type 2 diabetes. All participants underwent a hyperinsulinaemic–euglycaemic-(5.2 ± 0.4 mmol/L)-hypoglycaemic-(2.8 ± 0.13 mmol/L)-clamp. Results: The glucagon response was lower in people with type 1 diabetes (9.4 ± 0.8 pmol/L, 8.0 [7.0–10.0]) compared to type 2 diabetes (23.7 ± 3.7 pmol/L, 18.0 [12.0–28.0], p &lt; 0.001) and controls (30.6 ± 4.7, 25.5 [17.8–35.8] pmol/L, p &lt; 0.001). The adrenaline response was lower in type 1 diabetes (1.7 ± 0.2, 1.6 [1.3–5.2] nmol/L) compared to type 2 diabetes (3.4 ± 0.7, 2.6 [1.3–5.2] nmol/L, p = 0.001) and controls (2.7 ± 0.4, 2.8 [1.4–3.9] nmol/L, p = 0.012). Growth hormone was lower in people with type 2 diabetes than in type 1 diabetes, at baseline (3.4 ± 1.6 vs 7.7 ± 1.3 mU/L, p = 0.042) and during hypoglycaemia (24.7 ± 7.1 vs 62.4 ± 5.8 mU/L, p = 0.001). People with 1 diabetes had lower overall symptom responses than people with type 2 diabetes (45.3 ± 2.7 vs 58.7 ± 6.4, p = 0.018), driven by a lower neuroglycopenic score (27.4 ± 1.8 vs 36.7 ± 4.2, p = 0.012). Conclusion: Acute counterregulatory hormone and symptom responses to experimental hypoglycaemia are lower in people with type 1 diabetes than in those with long-standing insulin-treated type 2 diabetes and controls.</p

Association between recent exposure to continuous glucose monitoring-recorded hypoglycaemia and counterregulatory and symptom responses to subsequent controlled hypoglycaemia in people with type 1 diabetes

AimExperimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes.Materials and MethodsForty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project.ResultsCGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β −0.09, 95% CI (−0.16, −0.02) nmol/L, p = .014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [&lt;3.0 mmol/L (54 mg/dl)] [β −0.21, 95% CI (−0.41, −0.01) nmol/L, p = .034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders.ConclusionsRecent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes

Association between recent exposure to continuous glucose monitoring-recorded hypoglycaemia and counterregulatory and symptom responses to subsequent controlled hypoglycaemia in people with type 1 diabetes

AimExperimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes.Materials and MethodsForty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project.ResultsCGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β −0.09, 95% CI (−0.16, −0.02) nmol/L, p = .014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [&lt;3.0 mmol/L (54 mg/dl)] [β −0.21, 95% CI (−0.41, −0.01) nmol/L, p = .034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders.ConclusionsRecent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes

Activation of proteinase 3 contributes to Non-alcoholic Fatty Liver Disease (NAFLD) and insulin resistance

Contains fulltext : 169891.pdf (publisher's version ) (Open Access)Activation of inflammatory pathways is known to accompany development of obesity-induced non-alcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes. In addition to caspase-1, the neutrophil serine proteases proteinase 3, neutrophil elastase and cathepsin G are able to process the inactive pro-inflammatory mediators IL-1beta and IL-18 to their bioactive forms, thereby regulating inflammatory responses. In the present study, we investigated whether proteinase 3 is involved in obesity-induced development of insulin resistance and NAFLD. We investigated the development of NAFLD and insulin resistance in mice deficient for neutrophil elastase/proteinase 3 and neutrophil elastase/cathepsin G and in wild-type mice treated with the neutrophil serine proteinase inhibitor human alpha-1 antitrypsin. Expression profiling of metabolically relevant tissues obtained from insulin resistant mice showed that expression of proteinase 3 was specifically upregulated in the liver, whereas neutrophil elastase, cathepsin G and caspase-1 were not. Neutrophil elastase/proteinase 3 deficient mice showed strongly reduced levels of lipids in the liver after fed a high fat diet. Moreover, these mice were resistant to high fat diet-induced weight gain, inflammation and insulin resistance. Injection of proteinase 3 exacerbated insulin resistance in caspase-1(-/-) mice, indicating that proteinase 3 acts independently of caspase-1. Treatment with alpha-1 antitrypsin during the last 10 days of a 16 week high fat diet reduced hepatic lipid content and decreased fasting glucose levels. We conclude that proteinase 3 is involved in NAFLD and insulin resistance and that inhibition of proteinase 3 may have therapeutic potential

A Single Bout of High-Intensity Interval Training Reduces Awareness of Subsequent Hypoglycemia in Patients with Type 1 Diabetes.

High-intensity interval training (HIIT) gains increasing popularity in patients with diabetes. HIIT acutely increases plasma lactate levels. This may be important, since administration of lactate during hypoglycemia suppresses symptoms and counterregulation, whilst preserving cognitive function. We tested the hypothesis that HIIT acutely reduces awareness of hypoglycemia and attenuates hypoglycemia-induced cognitive dysfunction. In a randomized crossover trial, patients with type 1 diabetes and normal awareness of hypoglycemia (NAH), patients with impaired awareness of hypoglycemia (IAH), and healthy participants (n=10 per group) underwent a hyperinsulinemic-hypoglycemic (2.6 mmol/L) clamp, either after a HIIT session or after seated rest. Compared to rest, HIIT reduced symptoms of hypoglycemia in patients with NAH, but not in healthy participants or patients with IAH. HIIT attenuated hypoglycemia-induced cognitive dysfunction, which was mainly driven by changes in the NAH subgroup. HIIT suppressed cortisol and growth hormone responses, but not catecholamine responses to hypoglycemia. The present findings demonstrate that a single HIIT session rapidly reduces awareness of subsequent hypoglycemia in patients with type 1 diabetes and NAH, but not in patients with IAH, and attenuates hypoglycemia-induced cognitive dysfunction. The role of exercise-induced lactate in mediating these effects, potentially serving as an alternative fuel for the brain, should be further explored