Acute, same-day effects of antecedent exercise on counterregulatory responses to subsequent hypoglycemia in type 1 diabetes mellitus

2006 ◽  
Vol 290 (6) ◽  
pp. E1331-E1338 ◽  
Author(s):  
Darleen A. Sandoval ◽  
Deanna L. Aftab Guy ◽  
M. Antoinette Richardson ◽  
Andrew C. Ertl ◽  
Stephen N. Davis
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Muscle Sympathetic Nerve Activity ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Moderate Intensity ◽  
Endogenous Glucose ◽  
Exercise Induced

Exercise-induced hypoglycemia can occur within hours after exercise in type 1 diabetes mellitus (T1DM) patients. This study tested the hypothesis that an acute exercise bout causes (within hours) blunted autonomic and metabolic responses to subsequent hypoglycemia in patients with T1DM. Twelve T1DM patients (3 W/9 M) were studied during a single-step, 2-h hyperinsulinemic (572 ± 4 pmol/l) hypoglycemic (2.8 ± 0.1 mmol/l) clamp 2 h after either a hyperinsulinemic euglycemic (AM EUG) or hypoglycemic clamp (AM HYPO) or after sitting in a chair with basal insulin infusion (AM CON) or 90 min of moderate-intensity exercise (50% V̇o2 max, AM EX). Both AM HYPO and AM EX significantly blunted epinephrine responses and muscle sympathetic nerve activity responses to subsequent hypoglycemia compared with both control groups. Endogenous glucose production was significantly lower and the exogenous glucose infusion rate needed to maintain the hypoglycemic level was significantly greater during subsequent hypoglycemia in AM EX vs. CON. Rate of glucose disposal (Rd) was significantly reduced following AM HYPO. In summary, within 2.5 h, both moderate-intensity AM EX and AM HYPO blunted key autonomic counterregulatory responses. Despite this, glucose Rdwas reduced during afternoon hypoglycemia following morning hypoglycemia, indicating posthypoglycemic insulin resistance. After morning exercise, endogenous glucose production was blunted, but glucose Rdwas maintained during afternoon hypoglycemia, thereby indicating reduced metabolic defenses against hypoglycemia. These data suggest that exercise-induced counterregulatory failure can occur very rapidly, increasing the risk for hypoglycemia in T1DM within hours.

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 The Effect of a Short Sprint on Postexercise Whole-Body Glucose Production and Utilization Rates in Individuals with Type 1 Diabetes Mellitus

2012 ◽  
Vol 97 (11) ◽  
pp. 4193-4200 ◽  
Author(s):  
A. J. Fahey ◽  
N. Paramalingam ◽  
R. J. Davey ◽  
E. A. Davis ◽  
T. W. Jones ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Blood Glucose ◽  
Type 1 Diabetes Mellitus ◽  
Whole Body ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Glucose Levels ◽  
Blood Glucose Levels

Context: Recently we showed that a 10-sec maximal sprint effort performed before or after moderate intensity exercise can prevent early hypoglycemia during recovery in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms underlying this protective effect of sprinting are still unknown. Objective: The objective of the study was to test the hypothesis that short duration sprinting increases blood glucose levels via a disproportionate increase in glucose rate of appearance (Ra) relative to glucose rate of disappearance (Rd). Subjects and Experimental Design: Eight T1DM participants were subjected to a euglycemic-euinsulinemic clamp and, together with nondiabetic participants, were infused with [6,6-2H]glucose before sprinting for 10 sec and allowed to recover for 2 h. Results: In response to sprinting, blood glucose levels increased by 1.2 ± 0.2 mmol/liter (P < 0.05) within 30 min of recovery in T1DM participants and remained stable afterward, whereas glycemia rose by only 0.40 ± 0.05 mmol/liter in the nondiabetic group. During recovery, glucose Ra did not change in both groups (P > 0.05), but glucose Rd in the nondiabetic and diabetic participants fell rapidly after exercise before returning within 30 min to preexercise levels. After sprinting, the levels of plasma epinephrine, norepinephrine, and GH rose transiently in both experimental groups (P < 0.05). Conclusion: A sprint as short as 10 sec can increase plasma glucose levels in nondiabetic and T1DM individuals, with this rise resulting from a transient decline in glucose Rd rather than from a disproportionate rise in glucose Ra relative to glucose Rd as reported with intense aerobic exercise.

scholarly journals Hormone-independent activation of EGP during hypoglycemia is absent in type 1 diabetes mellitus

2000 ◽  
Vol 278 (3) ◽  
pp. E421-E429 ◽  
Author(s):  
Michèle Mevorach ◽  
Jonathan Kaplan ◽  
Chee Jen Chang ◽  
Luciano Rossetti ◽  
Harry Shamoon
Keyword(s):  
Diabetes Mellitus ◽  
Growth Hormone ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Endogenous Glucose Production ◽  
Experimental Protocol ◽  
Lower Plasma ◽  
The Face ◽  
Endogenous Glucose

It has been suggested that insulin-induced suppression of endogenous glucose production (EGP) may be counteracted independently of increased epinephrine (Epi) or glucagon during moderate hypoglycemia. We examined EGP in nondiabetic ( n = 12) and type 1 diabetic (DM1, n = 8) subjects while lowering plasma glucose (PG) from clamped euglycemia (5.6 mmol/l) to values just above the threshold for Epi and glucagon secretion (3.9 mmol/l). Individualized doses of insulin were infused to maintain euglycemia during pancreatic clamps by use of somatostatin (250 μg/h), glucagon (1.0 ng ⋅ kg− 1 ⋅ min− 1), and growth hormone (GH) (3.0 ng ⋅ kg− 1 ⋅ min− 1) infusions without need for exogenons glucose. Then, to achieve physiological hyperinsulinemia (HIns), insulin infusions were fixed at 20% above the rate previously determined for each subject. In nondiabetic subjects, PG was reduced from 5.4 ± 0.1 mmol/l to 3.9 ± 0.1 mmol/l in the experimental protocol, whereas it was held constant (5.3 ± 0.2 mmol/l and 5.5 mmol/l) in control studies. In the latter, EGP (estimated by [3-3H]glucose) fell to values 40% of basal ( P < 0.01). In contrast, in the experimental protocol, at comparable HIns but with PG at 3.9 ± 0.1 mmol/l, EGP was activated to values about twofold higher than in the euglycemic control ( P < 0.01). In DM1 subjects, EGP failed to increase in the face of HIns and PG = 3.9 ± 0.1 mmol/l. The decrease from basal EGP in DM1 subjects (4.4 ± 1.0 μmol ⋅ kg− 1 ⋅ min− 1) was nearly twofold that in nondiabetics (2.5 ± 0.8 μmol ⋅ kg− 1 ⋅ min− 1, P < 0.02). When PG was lowered further to frank hypoglycemia (∼3.1 mmol/l), the failure of EGP activation in DM1 subjects was even more profound but associated with a 50% lower plasma Epi response ( P < 0.02) compared with nondiabetics. We conclude that glucagon- or epinephrine-independent activation of EGP may accompany other counterregulatory mechanisms during mild hypoglycemia in humans and is impaired or absent in DM1.

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.

scholarly journals Long-Term Improvement in Glucose Control and Counterregulation by Islet Transplantation for Type 1 Diabetes

2016 ◽  
Vol 101 (11) ◽  
pp. 4421-4430 ◽  
Author(s):  
Michael R. Rickels ◽  
Amy J. Peleckis ◽  
Eileen Markmann ◽  
Cornelia Dalton-Bakes ◽  
Stephanie M. Kong ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
University Of Pennsylvania ◽  
Symptom Recognition ◽  
Endogenous Glucose ◽  
The University

Context: Islet transplantation has been shown to improve glucose counterregulation and hypoglycemia symptom recognition in patients with type 1 diabetes (T1D) complicated by severe hypoglycemia episodes and symptom unawareness, but long-term data are lacking. Objective: To assess the long-term durability of glucose counterregulation and hypoglycemia symptom responses 18 months after intrahepatic islet transplantation and associated measures of glycemic control during a 24-month follow-up period. Design, Setting, and Participants: Ten patients with T1D disease duration of approximately 27 years were studied longitudinally before and 6 and 18 months after transplant in the Clinical & Translational Research Center of the University of Pennsylvania and were compared to 10 nondiabetic control subjects. Intervention: All 10 patients underwent intrahepatic islet transplantation according to the CIT07 protocol at the Hospital of the University of Pennsylvania. Main Outcome Measures: Counterregulatory hormone, endogenous glucose production, and autonomic symptom responses derived from stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-2H2-glucose. Results: Near-normal glycemia (HbA1c ≤ 6.5%; time 70–180 mg/dL ≥ 95%) was maintained for 24 months in all patients, with one returning to low-dose insulin therapy. In response to insulin-induced hypoglycemia, glucagon secretion was incompletely restored at 6 and 18 months, epinephrine was improved at 6 months and normalized at 18 months, and endogenous glucose production and symptoms, absent before, were normalized at 6 and 18 months after transplant. Conclusions: In patients with T1D experiencing problematic hypoglycemia, intrahepatic islet transplantation can lead to long-term improvement of glucose counterregulation and hypoglycemia symptom recognition, physiological effects that likely contribute to glycemic stability after transplant.

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.

Effect of intermittent high-intensity compared with continuous moderate exercise on glucose production and utilization in individuals with type 1 diabetes

2007 ◽  
Vol 292 (3) ◽  
pp. E865-E870 ◽  
Author(s):  
K. J. Guelfi ◽  
N. Ratnam ◽  
G. A. Smythe ◽  
T. W. Jones ◽  
P. A. Fournier
Keyword(s):  
Type 1 Diabetes ◽  
High Intensity ◽  
Activity Patterns ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Moderate Intensity ◽  
Moderate Intensity Exercise ◽  
Early Recovery ◽  
Lower Glucose

Previously, the decline in glycemia in individuals with type 1 diabetes has been shown to be less with intermittent high-intensity exercise (IHE) compared with continuous moderate-intensity exercise (MOD) despite the performance of a greater amount of total work. The purpose of the present study was to determine whether this lesser decline in glycemia can be attributed to a greater increment in endogenous glucose production (Ra) or attenuated glucose utilization (Rd). Nine individuals with type 1 diabetes were tested on two separate occasions, during which either a 30-min MOD or IHE protocol was performed under conditions of a euglycemic clamp in combination with the infusion of [6,6-2H]glucose. MOD consisted of continuous cycling at 40% V̇o2 peak, whereas IHE involved a combination of continuous exercise at 40% V̇o2 peak interspersed with additional 4-s maximal sprint efforts performed every 2 min to simulate the activity patterns of intermittent sports. During IHE, glucose Ra increased earlier and to a greater extent compared with MOD. Similarly, glucose Rd increased sooner during IHE, but the increase by the end of exercise was comparable with that elicited by MOD. During early recovery from IHE, Rd rapidly declined, whereas it remained elevated after MOD, a finding consistent with a lower glucose infusion rate during early recovery from IHE compared with MOD ( P < 0.05). The results suggest that the lesser decline in glycemia with IHE may be attributed to a greater increment in Ra during exercise and attenuated Rd during exercise and early recovery.

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