RESUMO
AIM: Some people with type 2 diabetes mellitus (T2D) and declining ß-cell function do require insulin over time. Various laboratory parameters, indices of glucose metabolism or phenotypes of T2D (clusters) have been suggested, which might predict future therapy failure (TF), indicating the need for insulin therapy initiation. This analysis evaluated glycated haemoglobin (HbA1c), homeostatic model assessment (HOMA)2-B, C-peptide to glucose ratio (CGR) and diabetes clusters as predictive parameters for the occurrence of glycaemic TF in individuals diagnosed with T2D without previous insulin therapy. MATERIALS AND METHODS: In total, 159 individuals with T2D [41% female, median age 50 (IQR: 53-69) years, diabetes duration 9 (5-15) years], without insulin therapy were prospectively evaluated for the occurrence of a composite primary endpoint, including HbA1c increasing or remaining >8.0% (64 mmol/mol) 3 months after baseline on non-insulin glucose-lowering agents, insulin initiation or hospital admissions because of acute hyperglycaemic events. Diabetes clusters were formed according to previously described characteristics. Only severe autoimmune diabetes clusters were excluded because of a small amount of glutamate decarboxylase antibody-positive participants. The other clusters were distributed as mild age-related diabetes 33%; severe insulin-deficient diabetes 31%; mild obesity-related diabetes 20%; and severe insulin-resistant diabetes 15%. RESULTS: During a median observation of 57 months, higher tertiles of HbA1c at baseline, HOMA2-B, as well as a lower CGR were significantly predictive for the occurrence of the primary endpoint. The probability of meeting the primary endpoint was the highest for mild obesity-related diabetes [hazard ratio 3.28 (95% confidence interval 1.75-6.2)], followed by severe insulin-deficient diabetes [hazard ratio 2.03 (95% confidence interval 1.1-3.7)], mild age-related diabetes and the lowest for severe insulin-resistant diabetes. The best performance to predict TF with an area under the curve (AUC) of 0.77 was HbA1c at baseline, followed by HOMA2-B (AUC 0.69) and CGR (AUC 0.64). CONCLUSION: HbA1c, indices of insulin secretion capacity (HOMA2-B and CGR) and T2D clusters might be applicable tools to guide practitioners in the decision of whether insulin is required in people already diagnosed with T2D. These findings need to be validated in prospective studies.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glicemia/metabolismo , Peptídeo C , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Glucose , Hemoglobinas Glicadas , Insulina/uso terapêutico , Insulina/metabolismo , Resistência à Insulina/fisiologia , Insulina Regular Humana , Obesidade/complicações , Estudos Prospectivos , Sistema de Registros , IdosoRESUMO
Oxidative stress is involved in the development, progression, and complications of diabetes mellitus (DM). Oxidative modification of human serum albumin's cysteine-34 is a marker for oxidative stress-related pathological conditions. We aimed to evaluate the redox state of albumin in patients with DM to investigate possible correlations with age, diabetes duration, and disease control status. Plasma aliquots were collected from 52 participants (26 type 1 and 26 type 2 DM). Patients were divided into two groups according to their glycated hemoglobin levels less than or equal to and greater than 58 mmol/L. Albumin redox state was assessed with high-performance liquid chromatography by fractionating it into human mercaptalbumin (HMA) and human nonmercaptalbumin 1 and 2 (HNA1 and HNA2). Albumin redox fractions were differently related to the age of study participants. In age-matched T1DM and T2DM groups, the albumin redox state was essentially the same. Irreversibly oxidized HNA2 was positively correlated with diabetes duration, especially in the T1DM group. HNA was increased in people with an increased HbA1c (>58 mmol/mol). Our results support the hypothesis that oxidative stress plays a crucial role in DM pathogenesis and emphasize the importance of diabetes control on systemic oxidative burden.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Hemoglobinas Glicadas , Albumina Sérica Humana/metabolismo , Soro/metabolismo , Estresse Oxidativo , OxirreduçãoRESUMO
Lipoprotein(a) (Lp(a)) is considered an independent risk factor for cardiovascular diseases. The plasma concentration of Lp(a) is largely genetically determined but varies over a wide range within the population. This study investigated changes in Lp(a) levels after an acute myocardial infarction. Patients who underwent coronary angiography due to an ST elevation myocardial infarction were enrolled (n = 86), and Lp(a) levels were measured immediately after the intervention, one day, two days, and at a post-discharge follow-up visit at 3 to 6 months after the acute myocardial infarction. Median Lp(a) levels increased from a median of 7.9 mg/dL (3.8-37.1) at hospital admission to 8.4 mg/dL (3.9-35.4) on the following day, then to 9.3 mg/dL (3.7-39.1) on day two (p < 0.001), and to 11.2 mg/dL (4.4-59.6) at the post-discharge follow-up (p < 0.001). Lp(a) levels were the lowest during the acute myocardial infarction and started to increase significantly immediately thereafter, with the highest levels at the post-discharge follow-up. The moderate but significant increase in Lp(a) in people with acute myocardial infarction appears to be clinically relevant on an individual basis, especially when specific Lp(a) cut-off levels are supposed to determine the initiation of future treatment. Hence, a repeated measurement of Lp(a) after myocardial infarction should be performed.
Assuntos
Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Lipoproteína(a) , Assistência ao Convalescente , Biomarcadores , Alta do Paciente , Fatores de RiscoRESUMO
Metabolic regulation of glucose can be altered by fasting periods. We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 ± 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (p < 0.05). In non-obese participants, glucose levels were significantly higher after 36 h compared to 12 h fasting at 120 min of OGTT (109 ± 31 mg/dL vs. 79 ± 18 mg/dL; p = 0.001) but insulin levels were lower after 36 h of fasting at 30 min of OGTT (41.2 ± 34.1 mU/L after 36 h vs. 56.1 ± 29.7 mU/L; p < 0.05). In contrast, no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 h fasting. In line, metabolomics revealed subtle baseline differences and an attenuated metabolic response to fasting in obese participants and people with diabetes. Our data demonstrate an improved insulin sensitivity after 36 h of fasting with higher glucose variations and reduced early insulin response in non-obese people only.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Obesidade , Insulina/metabolismo , Glucose/metabolismo , Jejum , Glicemia/metabolismoRESUMO
Aims: In the ULTRAFLEXI-1 study, we compared basal insulin Glargine 300 U/mL (IGlar U300) and insulin Degludec 100 U/mL (IDeg U100) for time below range <70 mg/dL (TBR<70; 3.9 mmol/L) in two different doses (100% and 75% of the regular dose) when used around spontaneous exercise sessions in adults with type 1 diabetes. Methods: A randomized, single-center, four-period, cross-over trial was performed and in each of the four 2-weeks-periods, participants attended six spontaneous 60 min moderate-intensity evening cycle ergometer exercise sessions. The basal insulin administered on the exercise days were IGlar U300 100% or 75% of the regular dose or IDeg U100 100% or 75%, respectively (morning injection). The primary outcome was the TBR<70 during the 24 h postexercise periods of the six spontaneous exercise sessions in the four trial arms and was analyzed in hierarchical order using the repeated measures linear mixed model. Results: Twenty-five people with type 1 diabetes were enrolled (14 males) with a mean age of 41.4 ± 11.9 years and an HbA1c of 7.5% ± 0.8% (59 ± 9 mmol/mol). The mean ± standard error of mean TBR<70 during the 24 h periods following the exercise sessions was 2.71% ± 0.51% for IGlar U300 (100%) and 4.37% ± 0.69% for IDeg U100 (100%) (P = 0.023) as well as 2.28% ± 0.53% for IGlar U300 and 2.55% ± 0.58% for IDeg U100 when using a 75% dose on exercise days (P = 0.720). Time in glucose range70-180 was the highest in the IDeg U100 (100%) group. Conclusions: TBR<70 within the first 24 h after spontaneous exercise sessions was significantly lower when receiving IGlar U300 compared to IDeg U100 when a regular basal dose was administered.
Assuntos
Diabetes Mellitus Tipo 1 , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Insulina Glargina , Hipoglicemiantes , Estudos Cross-Over , GlicemiaRESUMO
OBJECTIVE: To investigate the safety and feasibility of 3 nonconsecutive days of intermittent fasting (IF) per week over 12 weeks in participants with insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: Forty-six people were randomized to an IF or control group. Dietary counseling and continuous glucose monitoring was provided. Coprimary end points were the change in HbA1c from baseline to 12 weeks and a composite end point (weight reduction ≥2%, insulin dose reduction ≥10%, and HbA1c reduction ≥3 mmol/mol). RESULTS: The IF group showed a significant HbA1c reduction (-7.3 ± 12.0 mmol/mol) compared with the control group (0.1 ± 6.1 mmol/mol) over 12 weeks (P = 0.012). The coprimary end point was achieved by 8 people in the IF and none in the control group (P < 0.001). No severe hypoglycemia occurred. CONCLUSIONS: IF is a safe and feasible dietary option to ameliorate glycemic control while reducing total daily insulin dose and body weight in insulin-treated people with type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Insulina , Jejum Intermitente , Humanos , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêuticoRESUMO
AIM: Intermittent fasting, a dietary intervention of alternate eating and fasting, has gained popularity in people trying to lose weight. Intermittent fasting could provide an alternative to classic caloric restriction in people with type 2 diabetes mellitus. The aim of the study is to determine the impact of a 12-week intermittent fasting regimen compared with usual care in people with type 2 diabetes mellitus receiving insulin therapy. METHODS: This open, single-centre, randomized controlled trial investigates participants with type 2 diabetes mellitus on insulin therapy and a glycated haemoglobin A1c (HbA1c) of ≥53 mmol/mol (≥7.0%) and a minimum insulin dose of 0.3 IU/kg body weight per day. Participants are randomized in a 1:1 ratio to either 12 weeks of intermittent fasting or the standard care group. All participants receive dietary counselling, continuous glucose monitoring, measurement of the resting metabolic rate, an oral glucose tolerance test, body composition measurement via dual-energy X-ray absorptiometry and stool samples for microbiome analyses at the beginning and at the end of the intervention. Two co-primary outcomes (analysed in hierarchical order) were chosen for the study: (i) the difference in the change of HbA1c from baseline to 12 weeks and (ii) the difference in the number of participants achieving a combined end point encompassing a body weight reduction of at least 2%, an insulin dose reduction of at least 10% and an absolute HbA1c reduction of at least 3 mmol/mol (0.3%) between the two groups.
Assuntos
Diabetes Mellitus Tipo 2 , Glicemia/metabolismo , Automonitorização da Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Jejum , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Insulina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
AIMS: To investigate the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and to analyse the response in comparison to individuals without diabetes. MATERIALS AND METHODS: This prospective, multicentre cohort study analysed people with type 1 and type 2 diabetes and a glycated haemoglobin level ≤58 mmol/mol (7.5%) or >58 mmol/mol (7.5%), respectively, and healthy controls. Roche's Elecsys anti-SARS-CoV-2 S immunoassay targeting the receptor-binding domain was used to quantify anti-spike protein antibodies 7 to 14 days after the first and 14 to 21 days after the second vaccination. RESULTS: A total of 86 healthy controls were enrolled in the study, as well as 161 participants with diabetes, of whom 150 (75 with type 1 diabetes and 75 with type 2 diabetes) were eligible for the analysis. After the first vaccination, only 52.7% of participants in the type 1 diabetes group and 48.0% of those in the type 2 diabetes group showed antibody levels above the cut-off for positivity. Antibody levels after the second vaccination were similar in participants with type 1 diabetes, participants with type 2 diabetes and healthy controls after adjusting for age, sex and multiple testing (P > 0.05). Age (r = -0.45, P < 0.001) and glomerular filtration rate (r = 0.28, P = 0.001) were significantly associated with antibody response. CONCLUSIONS: Anti-SARS-CoV-2 S receptor-binding domain antibody levels after the second vaccination were comparable in healthy controls and in participants with type 1 and type 2 diabetes, irrespective of glycaemic control. Age and renal function correlated significantly with the extent of antibody levels.
Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Humanos , Imunidade Humoral , Estudos Prospectivos , VacinaçãoAssuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Vacinas contra COVID-19 , Humanos , SARS-CoV-2 , VacinaçãoRESUMO
People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (n = 41) and type 2 diabetes mellitus (n = 37). Blood sampling points were prior to vaccination and two weeks after the respective vaccination. Thrombelastometry measurements indicated moderately increased clot formation post-vaccination in people with type 1, as well as with type 2, diabetes: "Clot formation times" were significantly shorter, and both "maximum clot firmness" and "alpha angles" were significantly higher, as compared to the respective pre-vaccination values. Therefore, TEM parameters were not altered after vaccination in patients receiving ASA. Moreover, platelet aggregation was enhanced in people with type 1 diabetes, and plasma levels of D-Dimer were increased in people with type 2 diabetes, following COVID-19 vaccination. All other standard coagulation parameters, as well as thrombin generation, were not affected by the vaccination. The coagulation responses of people with diabetes to COVID-19 vaccination were only subclinical and comparable to those observed in healthy individuals. Our findings suggest that people with diabetes do not face an increased activation of the coagulation post-vaccination.
Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hemostáticos , Humanos , Vacinas contra COVID-19/efeitos adversos , Trombina , COVID-19/prevenção & controle , VacinaçãoRESUMO
Prolonged fasting has shown beneficial effects in healthy individuals and in people with chronic diseases. In type 1 diabetes, the effect or even the feasibility of fasting is unclear. We aimed to assess the impact and safety of prolonged fasting in adults with type 1 diabetes. Glycemia was assessed during overnight fasting (12 hours) vs. prolonged fasting (36 hours) via an intermittently-scanned continuous glucose monitoring system. Anthropometric data, metabolic and hormonal markers were compared between both trial arms. After each fasting period, a 75 g oral glucose tolerance test was performed and plasma glucose levels and hormones were assessed. Data were compared via paired t-tests and mixed-model regressions (p ≤ 0.05). Twenty individuals with type 1 diabetes (7 females) with a mean ± SD age of 35 ± 11 years, body mass index (BMI) 24.8 ± 2.8 kg/m2 and HbA1c 54 ± 7 mmol/mol were included. Hypoglycemia/hour (70 mg/dL; <3.9 mmol/L) was similar in both trial arms (12 hrs: 0.07 ± 0.06 vs. 36 hrs: 0.05 ± 0.03, p=0.21). Glycemic excursions during the oral glucose tolerance test were not different after the two fasting periods. Beta-hydroxybutyrate levels were higher after prolonged fasting (p=0.0006). Our study showed that people with type 1 diabetes can safely perform a 36 hours fasting period with a low risk of hypoglycemia and ketoacidosis. Clinical Trial Registration: DRKS.de, identifier DRKS00016148.
Assuntos
Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/fisiopatologia , Jejum , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Adulto , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , PrognósticoRESUMO
The EndoBarrier™ medical device is a duodenal-jejunal bypass liner designed to mimic the effects of gastric bypass surgery to induce weight loss and glycaemic improvement. In this study, 10 participants with type 2 diabetes mellitus (T2DM), a mean body mass index (BMI) of 43.3 ± 5.0 (kg/m2) and a mean glycated haemoglobin A1c (HbA1c) of 60.6 ± 8.6 mmol/mol were examined at baseline (before implantation of EndoBarrier™), 4 weeks after implantation, at 36 weeks (right before explantation) and 24 weeks after the removal of the device to explore the short and long-term effects on glucose metabolism. Besides a significant reduction in body weight and fat mass, EndoBarrier™ treatment significantly improved insulin sensitivity during Botnia clamp investigations after four weeks of implantation. The beneficial effects decreased over time but remained significant 24 weeks after removal of the device.
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Cirurgia Bariátrica/métodos , Diabetes Mellitus Tipo 2/cirurgia , Resistência à Insulina , Obesidade/cirurgia , Próteses e Implantes , Adiposidade , Adulto , Cirurgia Bariátrica/instrumentação , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Jejuno/cirurgia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Redução de PesoRESUMO
To assess intermittently scanned continuous glucose monitoring (isCGM) performance for different rates of change in plasma glucose (RCPG) during glycemic challenges in type 1 diabetes (T1D). Nineteen people with T1D (7 females; age 35 ± 11 years; HbA1c 7.3 ± 0.6% (56 ± 7 mmol/mol)) performing two glycemic challenges (OGTT) were included. During OGTTs, plasma glucose was compared against sensor glucose for timepoints 0 min (pre-OGTT), +15 min, +30 min, +60 min, +120 min, +180 min, and +240 min by means of median absolute (relative) difference (MARD and MAD) and Clarke Error Grid (CEG), then was stratified for RCPG and glycemic ranges. Overall, MARD was 8.3% (4.0-14.8) during hypoglycemia level 1 18.8% (15.8-22.0), euglycemia 9.5% (4.3-15.1), hyperglycemia level 1 9.4% (4.0-17.2), and hyperglycemia level 2 7.1% (3.3-11.9). The MARD was associated with the RCPG (p < 0.0001), detailing significant differences in comparison of low, moderate, high, and very high RCPG (p = 0.014). Overall, CEG resulted in 88% (212 values) of comparison points in zone A, 12% (29 values) in zone B, and 0.4% (1 value) in zone D. The isCGM system was accurate during OGTTs. Its performance was dependent on the RCPG and showed an overestimation of the actual reference glucose during hypoglycemia.
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Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Glucose/administração & dosagem , Administração Oral , Adulto , Automonitorização da Glicemia , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
To investigate differences in heart rate variability (HRV) during oral glucose tolerance tests (OGTTs) in response to the rate of change in glucose and to different glycaemic ranges in individuals with type 1 diabetes. This was a single-centre, prospective, secondary outcome analysis in 17 individuals with type 1 diabetes (glycated haemoglobin 53 ± 6.3 mmol/L), who underwent two OGTTs (after 12 and 36 hours of fasting) investigating differences in HRV in response to rapid glucose increases/decreases and different glycaemic ranges during OGTT. Based on the rate of change in glucose level, the variables heart rate (P < 0.001), square root of the mean standard difference of successive R-R intervals (P = 0.002), percentage of pairs of R-R intervals with >50 ms difference (P < 0.001) and corrected QT interval (P = 0.04) were significantly altered, with HRV particularly reduced during episodes of rapid glucose rises. Glycaemic ranges during OGTT had no impact on HRV (P < 0.05). Individuals with type 1 diabetes showed no changes in HRV in response to different glycaemic ranges. HRV was dependent on the rate of change in glucose, especially rapid increases in glucose level.
Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Sistema Nervoso Autônomo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose , Frequência Cardíaca , Humanos , Estudos ProspectivosRESUMO
INTRODUCTION: To investigate the glycaemic response, macronutrient intake and insulin management in people with type 1 diabetes (T1D) compared to healthy individuals around a running competition. MATERIAL AND METHODS: This was a single-centre, prospective, controlled observational study performed in individuals with T1D and healthy people. 24 people (12 T1D) were included in this study (age: T1D 41±12 vs. healthy 38±6 years, females: 3 vs. 6, BMI: 25.53.0 vs. 22.9±2.8 kg/m2). Both groups received an intermittently scanned continuous glucose monitoring (isCGM; FreeStyle Libre 1, Abbott, USA) system to assess glycaemia 24 hours before, during and 24 hours after a running competition. During this period, participants recorded their food intake and insulin administration. Data were analysed via ANOVA and mixed model analyses with post-hoc testing (p≤0.05). RESULTS: For overall glycaemic ranges in comparison of groups, significant differences were found for time in range (T1D 63±21% vs. healthy 89±13%, p = 0.001), time above range (TAR) 1 (T1D 21±15% vs. healthy 0±0%, p<0.001) and TAR 2 (T1D 8 [0-16%] vs. healthy 0±0%, p<0.001). When glycaemic variability was assessed, people with T1D had a higher glycaemic variability compared to healthy individuals (p<0.0001). Basal insulin dose was significantly reduced when compared against the regular pre-study basal insulin dose (pre-study 22±6 vs. pre-competition day 11±9 (-50±41%), p = 0.02; competition day 15±5 (-32± 1%)). CONCLUSION: People with T1D have impaired glucose responses around a running competition compared to healthy individuals. However, basal insulin dose reductions were sufficient to prevent further dysglycaemia. CLINICAL TRIAL ID: drks.de; DRKS00019886.
Assuntos
Glicemia/fisiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Ingestão de Alimentos/fisiologia , Insulina/administração & dosagem , Corrida/fisiologia , Adolescente , Adulto , Idoso , Glicemia/análise , Glicemia/efeitos dos fármacos , Automonitorização da Glicemia/estatística & dados numéricos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
AIMS: To investigate the effect of hypoglycaemia on platelet and coagulation activation in people with type 2 diabetes. MATERIALS AND METHODS: This monocentric, open, single-arm, mechanistic trial included 14 people with established type 2 diabetes (four women, 10 men, age 55 ± 7 years, glycated haemoglobin concentration 51 ± 7 mmol/mol) receiving metformin monotherapy. A stepwise hyperinsulinaemic-hypoglycaemic clamp experiment (3.5 and 2.5 mmol/L, for 30 minutes respectively) was performed, aiming to investigate platelet and coagulation activity during predefined plateaus of hypoglycaemia, as well as 1 day and 7 days later. RESULTS: While platelet activation assessed by light transmittance aggregometry did not significantly increase after the hypoglycaemic clamp procedure, the more sensitive flow cytometry-based measurement of platelet surface activation markers showed hypoglycaemia-induced activation 24 hours (PAC1pos CD62Ppos , PAC1pos CD63Ppos and PAC1pos CD62Ppos CD63pos ; P < .01) and 7 days after the hypoglycaemic clamp (P < .001 for PAC1pos CD63pos ; P < .01 for PAC1pos CD62Ppos and PAC1pos CD62Ppos CD63pos ) in comparison to baseline. Coagulation markers, such as fibrinogen, D-dimer, plasminogen activator inhibitor-1, von Willebrand factor activity and factor VIII, were also significantly increased, an effect that was most pronounced 24 hours after the hypoglycaemic clamp. CONCLUSION: A single event of insulin-induced hypoglycaemia led to an increase in markers of platelet activation and coagulation in people with early stages of type 2 diabetes on metformin therapy. However, the activation occurred with a delay and was evident 24 hours and 7 days after the actual hypoglycaemic episode.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/sangue , Metformina/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Testes de Coagulação Sanguínea , Diabetes Mellitus Tipo 2/sangue , Feminino , Técnica Clamp de Glucose/métodos , Humanos , Hipoglicemia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
The aim of the study was to assess the amount of orally administered carbohydrates needed to maintain euglycemia during moderate-intensity exercise in individuals with type 1 diabetes. Nine participants with type 1 diabetes (four women, age 32.1 ± 9.0 years, BMI 25.5 ± 3.9 kg/m2, HbA1c 55 ± 7 mmol/mol (7.2 ± 0.6%)) on insulin Degludec were randomized to cycle for 55 min at moderate intensity (63 ± 7% VO2peak) for five consecutive days on either 75% or 100% of their regular basal insulin dose. The impact of pre-exercise blood glucose concentration on the carbohydrate requirement was analyzed by one-way ANOVA stratified for pre-exercise blood glucose quartiles. The effect of the basal insulin dose on the amount of orally administered carbohydrates was evaluated by Wilcoxon matched-pairs signed-rank test. The amount of orally administered carbohydrates during the continuous exercise sessions was similar for both trial arms (75% or 100% basal insulin) with median [IQR] of 36 g (9-62 g) and 36 g (9-66 g) (p = 0.78). The amount of orally administered carbohydrates was determined by pre-exercise blood glucose concentration for both trial arms (p = 0.03). Our study elucidated the importance of pre-exercise glucose concentration related orally administered carbohydrates to maintain euglycemia during exercise in individuals with type 1 diabetes.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Carboidratos da Dieta/administração & dosagem , Exercício Físico/fisiologia , Hipoglicemia/prevenção & controle , Adulto , Ciclismo , Estudos Cross-Over , Carboidratos da Dieta/sangue , Feminino , Humanos , Hipoglicemia/sangue , Insulina/administração & dosagem , Masculino , Consumo de Oxigênio , Adulto JovemRESUMO
OBJECTIVE: To evaluate the experiences of families with very young children aged 1 to 7 years (inclusive) with type 1 diabetes using day-and-night hybrid closed-loop insulin delivery. METHODS: Parents/caregivers of 20 children aged 1 to 7 years with type 1 diabetes completed a closed-loop experience survey following two 3-week periods of unrestricted day-and-night hybrid closed-loop insulin therapy using Cambridge FlorenceM system at home. Benefits, limitations, and improvements of closed-loop technology were explored. RESULTS: Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed-loop. Ninety percent of the responders felt less worried about their child's glucose control using closed-loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets. CONCLUSIONS: Parents/caregivers of very young children reported important quality of life benefits associated with using closed-loop, supporting adoption of this technology in this population.