Effects of glycemic control on target organ responses to epinephrine in type 1 diabetes

2005 ◽  
Vol 289 (2) ◽  
pp. E258-E265 ◽  
Author(s):  
Deanna Aftab Guy ◽  
Darleen Sandoval ◽  
M. A. Richardson ◽  
Donna Tate ◽  
Stephen N. Davis
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Blood Pressure Response ◽  
Severe Hypoglycemia ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Target Organ ◽  
Epinephrine Infusion ◽  
Glucose Levels

Severe hypoglycemia occurs in intensively treated patients with type 1 diabetes mellitus (T1DM) due in part to deficient epinephrine counterregulatory responses. Previously, we have found that T1DM patients demonstrated a spectrum of altered responses to epinephrine at a variety of target organs compared with nondiabetic healthy subjects. What is not known is whether intensive glycemic control further modifies target organ responses in individuals with T1DM. Therefore, the aim of this study is to assess whether there is tissue specific (liver, muscle, adipose tissue, pancreas and cardiovascular) resistance to epinephrine in intensively controlled (IC) T1DM compared with those with conventional control (CC). Eight IC patients (age 33 ± 4 yr, BMI 24 ± 2 kg/m2, Hb A1C6.7 ± 0.1%), and 11 CC patients (age 35 ± 3 yr, BMI 25 ± 1 kg/m2, Hb A1C9.6 ± 0.1%) underwent two separate randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (EPI) and without (NO EPI) epinephrine infusion. Epinephrine levels during EPI were similar in all groups (5,197 ± 344 pmol/l). Glucose (5.3 ± 0.1 mmol/l) and insulin levels (515 ± 44 pmol/l) were similar in all groups during the glucose clamps. Endogenous glucose production (EGP) and glucose uptake (Rd) were determined using [3-H3]glucose. Muscle biopsy was performed at the end of each study. IC had a significantly reduced EGP and Rdresponses to EPI compared with CC. Glucagon responses to EPI were similarly blunted in both IC and CC. Free fatty acid and glycerol response to EPI was greater in CC compared with IC. There was a significantly greater systolic blood pressure response to EPI in CC. We conclude that, despite similar epinephrine, insulin, and glucose levels, intensively treated T1DM patients had reduced cardiovascular, skeletal muscle, hepatic, and adipose target organ responses to EPI compared with conventionally treated T1DM patients.

Effect of differing antecedent hypoglycemia on counterregulatory responses to exercise in type 1 diabetes

2006 ◽  
Vol 290 (6) ◽  
pp. E1109-E1117 ◽  
Author(s):  
Pietro Galassetti ◽  
Donna Tate ◽  
Ray A. Neill ◽  
Antoinette Richardson ◽  
Szu-Yun Leu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Intermediary Metabolites ◽  
Glucose Levels ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Hypoglycemia frequently occurs during or after exercise in intensively treated patients with type 1 diabetes mellitus (T1DM), but the underlying mechanisms are not clear. In both diabetic and nondiabetic subjects, moderate hypoglycemia blunts counterregulatory responses to subsequent exercise, but it is unknown whether milder levels of hypoglycemia can exert similar effects in a dose-dependent fashion. This study was designed to test the hypothesis that prior hypoglycemia of differing depths induces acute counterregulatory failure of proportionally greater magnitude during subsequent exercise in T1DM. Twenty-two T1DM patients (11 males/11 females, HbA1c8.0 ± 0.3%) were studied during 90 min of euglycemic cycling exercise after two 2-h periods of previous day euglycemia or hypoglycemia of 3.9, 3.3, or 2.8 mmol/l (HYPO-3.9, HYPO-3.3, HYPO-2.8, respectively). Patients' counterregulatory responses (circulating levels of neuroendocrine hormones, intermediary metabolites, substrate flux, tracer-determined glucose kinetics, and cardiovascular measurements) were assessed during exercise. Identical euglycemia and basal insulin levels were successfully maintained during all exercise studies, regardless of blood glucose levels during the previous day. After day 1 euglycemia, patients displayed normal counterregulatory responses to exercise. Conversely, when identical exercise was performed after day 1 hypoglycemia of increasing depth, a progressively greater blunting of glucagon, catecholamine, cortisol, endogenous glucose production, and lipolytic responses to exercise was observed. This was paralleled by a graduated increase in the amount of exogenous glucose needed to maintain euglycemia during exercise. Our results demonstrate that acute counterregulatory failure during prolonged, moderate-intensity exercise may be induced in a dose-dependent fashion by differing depths of antecedent hypoglycemia starting at only 3.9 mmol/l in patients with T1DM.

scholarly journals Impact of Genetic Polymorphism in the β2-Receptor Gene on Risk of Severe Hypoglycemia in Patients With Type 1 Diabetes

2018 ◽  
Vol 103 (8) ◽  
pp. 2901-2908 ◽  
Author(s):  
Kim Zillo Rokamp ◽  
Niels Vidiendal Olsen ◽  
Louise Færch ◽  
Peter Lommer Kristensen ◽  
Birger Thorsteinsson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Polymorphism ◽  
Relative Rate ◽  
Receptor Gene ◽  
Severe Hypoglycemia ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Genotype Distribution ◽  
Validated Questionnaire

Abstract Context Severe hypoglycemic events are unevenly distributed in people with type 1 diabetes, making a genetic influence probable. Of the common adrenoceptor β-2 receptor gene (ADRB2) polymorphisms, the Arg16 allele is associated with receptor downregulation and reduced agonist-mediated endogenous glucose production. Objective We tested the hypothesis that the Arg16 variant is associated with severe hypoglycemia. Method A cohort of 311 patients with type 1 diabetes reported severe hypoglycemic events retrospectively in a validated questionnaire. The patients were characterized by diabetes history, state of hypoglycemia awareness, C-peptide status, HbA1c, and ADRB2 genotype. Results The ADRB2 Gly16Arg genotype distribution was in Hardy-Weinberg equilibrium. The rate of severe hypoglycemia differed among all genotypes (P = 0.01). Patients homozygous for the Arg16 genotype (AA; n = 60) had a relative rate (RR) of severe hypoglycemia of 2.2 (95% CI, 1.3 to 3.6) compared with patients homozygous for the Gly16 genotype (GG; n = 116; P = 0.002). Among patients with impaired awareness or unawareness (n = 175), those with the AA genotype (n = 33) had an RR of severe hypoglycemia of 3.2 (95% CI, 1.7 to 6.0) compared with patients with the GG genotype (n = 58; P < 0.000). Genotype was not associated with state of hypoglycemia awareness per se, as assessed by any of three classification methods. The difference was not explained by other risk factors. Conclusion Genetic polymorphism in ADRB2 is associated with risk of severe hypoglycemia in individuals with type 1 diabetes, especially in those with impaired hypoglycemia awareness.

691-P: Exercise Effect on Endogenous Glucose Production in Type 1 Diabetes: A Modeling Analysis

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 691-P
Author(s):  
DAVIDE ROMERES ◽  
MICHELE SCHIAVON ◽  
ROBERTO VISENTIN ◽  
ANANDA BASU ◽  
CLAUDIO COBELLI ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Modeling Analysis ◽  
Exercise Effect ◽  
Endogenous Glucose

scholarly journals Anxiety, depression, and glycemic control during Covid-19 pandemic in youths with type 1 diabetes

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maria Cusinato ◽  
Mariangela Martino ◽  
Alex Sartori ◽  
Claudia Gabrielli ◽  
Laura Tassara ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Psychological Impact ◽  
Glucose Monitoring ◽  
Severe Hypoglycemia ◽  
Well Being ◽  
Glucose Variability ◽  
Threshold Score ◽  
The Impact

Abstract Objectives Our study aims to assess the impact of lockdown during the coronavirus disease 2019 pandemic on glycemic control and psychological well-being in youths with type 1 diabetes. Methods We compared glycemic metrics during lockdown with the same period of 2019. The psychological impact was evaluated with the Test of Anxiety and Depression. Results We analyzed metrics of 117 adolescents (87% on Multiple Daily Injections and 100% were flash glucose monitoring/continuous glucose monitoring users). During the lockdown, we observed an increase of the percentage of time in range (TIR) (p<0.001), with a significant reduction of time in moderate (p=0.002), and severe hypoglycemia (p=0.001), as well as the percentage of time in hyperglycemia (p<0.001). Glucose variability did not differ (p=0.863). The glucose management indicator was lower (p=0.001). 7% of youths reached the threshold-score (≥115) for anxiety and 16% for depression. A higher score was associated with lower TIR [p=0.028, p=0.012]. Conclusions Glycemic control improved during the first lockdown period with respect to the previous year. Symptoms of depression and anxiety were associated with worse glycemic control; future researches are necessary to establish if this improvement is transient and if psychological difficulties will increase during the prolonged pandemic situation.

Type I Diabetes Mellitus

2019 ◽  
Author(s):  
Joseph I. Wolfsdorf ◽  
Katharine Garvey
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Autoimmune Diabetes ◽  
Type I ◽  
Insulin Deficiency ◽  
Glucose Levels

Type 1 diabetes mellitus is characterized by severe insulin deficiency, making patients dependent on exogenous insulin replacement for survival. These patients can experience life-threatening events when their glucose levels are significantly abnormal. Type 1 diabetes accounts for 5 to 10% of all diabetes cases, with type 2 accounting for most of the remainder. This review details the pathophysiology, stabilization and assessment, diagnosis and treatment, disposition and outcomes of patients with Type 1 diabetes mellitus. Figures show the opposing actions of insulin and glucagon on substrate flow and plasma levels; plasma glucose, insulin and C-peptide levels throughout the day; the structure of human proinsulin; current view of the pathogenesis of Type 1 autoimmune diabetes mellitus; pathways that lead from insulin deficiency to the major clinical manifestations of Type 1 diabetes mellitus; relationship between hemoglobin A1c values at the end of a 3-month period and calculated average glucose levels during the 3-month period; different combinations of various insulin preparations used to establish glycemic control; and basal-bolus and insulin pump regimens. Tables list the etiologic classification of Type 1 diabetes mellitus, typical laboratory findings and monitoring in diabetic ketoacidosis, criteria for the diagnosis of Type 1 diabetes, clinical goals of Type 1 diabetes treatment, and insulin preparations. This review contains 10 figures, 9 tables, and 40 references. Keywords: Type 1 diabetes mellitus, optimal glycemic control, hypoglycemia, hyperglycemia, polyuria, polydipsia, polyphagia, HbA1c, medical nutrition therapy, Diabetic Ketoacidosis

scholarly journals Glucagon sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments

2015 ◽  
Vol 309 (5) ◽  
pp. E474-E486 ◽  
Author(s):  
Ling Hinshaw ◽  
Ashwini Mallad ◽  
Chiara Dalla Man ◽  
Rita Basu ◽  
Claudio Cobelli ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
In Silico ◽  
Artificial Pancreas ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Action Model ◽  
The Difference ◽  
Hormone Control

Glucagon use in artificial pancreas for type 1 diabetes (T1D) is being explored for prevention and rescue from hypoglycemia. However, the relationship between glucagon stimulation of endogenous glucose production (EGP) viz., hepatic glucagon sensitivity, and prevailing glucose concentrations has not been examined. To test the hypothesis that glucagon sensitivity is increased at hypoglycemia vs. euglycemia, we studied 29 subjects with T1D randomized to a hypoglycemia or euglycemia clamp. Each subject was studied at three glucagon doses at euglycemia or hypoglycemia, with EGP measured by isotope dilution technique. The peak EGP increments and the integrated EGP response increased with increasing glucagon dose during euglycemia and hypoglycemia. However, the difference in dose response based on glycemia was not significant despite higher catecholamine concentrations in the hypoglycemia group. Knowledge of glucagon's effects on EGP was used to develop an in silico glucagon action model. The model-derived output fitted the obtained data at both euglycemia and hypoglycemia for all glucagon doses tested. Glucagon clearance did not differ between glucagon doses studied in both groups. Therefore, the glucagon controller of a dual hormone control system may not need to adjust glucagon sensitivity, and hence glucagon dosing, based on glucose concentrations during euglycemia and hypoglycemia.

scholarly journals Stigma and Its Association With Glycemic Control and Hypoglycemia in Adolescents and Young Adults With Type 1 Diabetes: Cross-Sectional Study (Preprint)

2017 ◽  
Author(s):  
Anne-Sophie Brazeau ◽  
Meranda Nakhla ◽  
Michael Wright ◽  
Mélanie Henderson ◽  
Constadina Panagiotopoulos ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Diabetes Management ◽  
Severe Hypoglycemia ◽  
Poor Glycemic Control ◽  
Self Report ◽  
Diabetes Diagnosis ◽  
Hypoglycemic Episode ◽  
Cross Sectional

BACKGROUND Qualitative studies in type 1 diabetes indicate that visibility of diabetes supplies, self-care, and hypoglycemia symptoms are associated with stigma and suboptimal management. This may be particularly salient in youth who face concurrent challenges such as establishing autonomy and making vocational choices. OBJECTIVE The aim of the study was to estimate stigma prevalence in youth (aged 14-24 years) with type 1 diabetes and its associations with glycemic control. METHODS Participants, recruited largely through social media, were asked to complete a Web-based survey and to send via mail capillary blood samples for glycated hemoglobin (HbA1c) measurement. The primary definition of stigma required endorsement of one or more of 3 stigma-specific items of the Barriers to Diabetes Adherence questionnaire. These addressed avoidance of diabetes management with friends present, difficulty telling others about diabetes diagnosis, and embarrassment in performing diabetes care with others present. Poor glycemic control was defined as HbA1c>9% (ie, >75 mmol/mol; measured value when available, else self-report) and/or ≥1 severe hypoglycemic episode in the previous year (reported requiring assistance from someone else during the episode). Stigma prevalence was computed (95% CI), and associations with glycemic control were evaluated (multivariate logistic regression models). RESULTS Among the 380 respondents, stigma prevalence was 65.5% (95% CI 60.7-70.3). Stigma was associated with a 2-fold higher odds of poor glycemic control overall (odds ratio [OR] 2.25, 95% CI 1.33-3.80; adjusted for age, sex, and type of treatment). There were specific associations with both HbA1c>9% (75 mmol/mol; OR 3.05, 95% CI 1.36-6.86) and severe hypoglycemia in the previous year (OR 1.86, 95% CI 1.05-3.31). CONCLUSIONS There is a high prevalence of stigma in youth with type 1 diabetes that is associated with both elevated HbA1c levels and severe hypoglycemia. Targeted strategies to address stigma are needed. CLINICALTRIAL ClinicalTrials.gov NCT02796248; http://clinicaltrials.gov/ct2/show/NCT02796248 (Archived by WebCite at http://www.webcitation.org/6yisxeV0B)

scholarly journals Effects of Growth Hormone and Free Fatty Acids on Insulin Sensitivity in Patients with Type 1 Diabetes

2009 ◽  
Vol 94 (9) ◽  
pp. 3297-3305 ◽  
Author(s):  
Burak Salgin ◽  
Maria L. Marcovecchio ◽  
Rachel M. Williams ◽  
Sarah J. Jackson ◽  
Leslie J. Bluck ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Growth Hormone ◽  
Type 1 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Endogenous Glucose

Context: Because GH stimulates lipolysis, an increase in circulating free fatty acid levels, as opposed to a direct effect of high GH levels, could underlie the development of insulin resistance in type 1 diabetes (T1D). Our aim was to explore the relative contributions of GH and free fatty acids to the development of insulin resistance in patients with T1D. Patients: Seven (four females, three males) nonobese patients with T1D aged 21–30 yr were studied on four occasions in random order. On each visit, overnight endogenous GH production was suppressed by octreotide. Three 1-h pulses of recombinant human GH (rhGH) or placebo were administered on two visits each. Acipimox, an antilipolytic drug, or a placebo were ingested every 4 h on two visits each. Stable glucose and glycerol isotopes were used to assess glucose and glycerol turnover. The overnight protocol was concluded by a two-step hyperinsulinemic euglycemic clamp on each visit. Main Outcome: rhGH administration led to increases in the insulin infusion rate required to maintain euglycemia overnight (P = 0.008), elevated basal endogenous glucose production (P = 0.007), decreased basal peripheral glucose uptake (P = 0.03), and reduced glucose uptake during step 1 of the clamp (P &lt; 0.0001). Coadministration of rhGH and acipimox reversed these effects and suppression of lipolysis in the absence of GH replacement led to further increases in insulin sensitivity. Results: GH pulses were associated with an increase in endogenous glucose production and decreased rates of peripheral glucose uptake, which was entirely reversed by acipimox. Therefore, GH-driven decreases in insulin sensitivity are mainly determined by the effect of GH on lipolysis. Growth hormone decreases insulin sensitivity through increases in free fatty acid levels.

Sign in / Sign up

Export Citation Format

Share Document