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Biomedical subjects

Stephen N Davis

Publications and source records attributed to Stephen N Davis.

At least 19 recordsLinked to original sources
PubMed2006

Autonomic contribution to blood pressure and metabolism in obesity.

Obesity is associated with alterations in the autonomic nervous system that may contribute to the increase in blood pressure and resting energy expenditure present in this condition. To test this hypothesis, we induced autonomic withdrawal with the ganglionic blocker trimethaphan in 10 lean (32+/-3 years) and 10 obese (35+/-3 years) subjects. Systolic blood pressure fell more in obese compared with lean subjects (-17+/-3 versus -11+/-1 mm Hg; P=0.019) because of a greater decrease in total peripheral resistance (-310+/-41 versus 33+/-78 dynes/sec/cm(-5); P=0.002). In contrast, resting energy expenditure decreased less in obese than in lean subjects, (-26+/-21 versus -86+/-15 kcal per day adjusted by fat-free mass; P=0.035). We confirmed that the autonomic contribution to blood pressure was greater in obesity after including additional subjects with a wider range of blood pressures. Systolic blood pressure decreased -28+/-4 mm Hg (95% CI: -38 to -18.0; n=8) in obese hypertensive subjects compared with lean (-9+/-1 mm Hg; 95% CI: -11 to -6; n=22) or obese normotensive subjects (-14+/-2 mm Hg; 95% CI: -18 to -10; n=20). After removal of autonomic influences, systolic blood pressure remained higher in obese hypertensive subjects (109+/-3 versus 98+/-2 mm Hg in lean and 103+/-2 mm Hg in obese normotensive subjects; P=0.004) suggesting a role for additional factors in obesity-associated hypertension. In conclusion, sympathetic activation induced by obesity is an important determinant to the blood pressure elevation associated with this condition but is not effective in increasing resting energy expenditure. These results suggest that the sympathetic nervous system could be targeted in the treatment of obesity-associated hypertension.

Adult↗
PubMed2006

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

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% Vo(2 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 Rd was reduced during afternoon hypoglycemia following morning hypoglycemia, indicating posthypoglycemic insulin resistance. After morning exercise, endogenous glucose production was blunted, but glucose Rd was 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.

Adult↗
PubMed2006

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

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, HbA1c 8.0 +/- 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.

Adult↗
PubMed2006

Early intervention to achieve optimal outcomes in type 2 diabetes: a case presentation.

Type 2 diabetes mellitus (DM) is a progressive disease characterized by insulin resistance and impaired insulin secretion. To compensate for these metabolic dysfunctions, pancreatic beta-cells begin to overproduce insulin; however, it is this compensatory mechanism that eventually results in beta-cell exhaustion, impaired insulin secretion, and relative insulin deficiency. The metabolic abnormalities associated with diabetes also contribute to vascular dysfunction and an increased risk of coronary heart disease. Among patients with type 2 DM, cardiovascular disease, particularly macrovascular disease, is the primary cause of mortality, accounting for 55% of deaths. Management of the disease, therefore, must address all of the contributing factors, including a sedentary lifestyle and diet that contribute to overweight/obesity, and comorbidities such as hypertension and dyslipidemia. In this paper, we present a case study based on actual clinical experience to illustrate an evidence-based rationale for early and aggressive intervention for patients with type 2 DM, including lifestyle modification, oral antidiabetic agents, and insulin.

Diabetes Mellitus, Type 2↗
PubMed2006

Overcoming psychological barriers to insulin use in type 2 diabetes.

Type 2 diabetes mellitus (DM) is characterized by a gradual decrease in insulin sensitivity in peripheral tissues and the liver (insulin resistance), followed by a gradual decline in beta-cell function and insulin secretion. Given this decline, many patients with type 2 DM will require insulin therapy to achieve the glycemic target recommended by the American Diabetes Association of glycosylated hemoglobin (A1C) <7%. The combination of insulin plus oral antidiabetic drugs (OADs) has been shown to improve A1C values in patients who were not adequately controlled with OADs alone. Despite its established benefits, however, insulin therapy continues to be underused. The reluctance to initiate insulin therapy is often related to both provider and patient misperceptions about insulin's efficacy and side effects, as well as the perceived complexity of the treatment regimen. In addition, insulin therapy may be viewed as a "last resort" treatment option for severe disease or as "punishment" for patients' failure to manage their disease. However, patients should be made aware from the time of diagnosis that diabetes is a progressive disease and that it is likely that insulin therapy will be required at some point during the course of the disease. The subject of insulin therapy, therefore, should be approached positively and should be presented as an effective and flexible way to achieve glycemic goals for any patient at any time during therapy.

Clinical Competence↗
PubMed2006

Metabolic consequences of exercise-associated autonomic failure.

Type I diabetes mellitus patients who tightly control blood glucose levels toward normal have increased frequency of hypoglycemia, a major barrier to physical activity. This article presents the hypothesis that dysfunctional autonomic regulation of metabolism after recent bouts of exercise or hypoglycemia contributes to exercise-induced hypoglycemia in these patients.

Autonomic Nervous System↗
PubMed2006

Contemporary strategies for managing cardiometabolic risk factors.

OBJECTIVE: To review the metabolic syndrome as defined by the 2001 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) and its modifiable risk factors and to review currently available treatment modalities. SUMMARY: Metabolic syndrome, although still controversial, is a growing concern. Most definitions include elevated blood pressure, smoking, inflammation, insulin resistance, abdominal adiposity, elevated blood glucose, and atherogenic dyslipidemia as modifiable risk factors. Some researchers believe that additional signs of inflammation such as plasminogen activator inhibitor-1 and C-reactive protein should be added to this list. Current treatment options include lifestyle changes (diet and exercise), pharmacotherapy, and bariatric surgery. The endocannabinoid system appears to play a key role in metabolism and weight gain. The investigational agent rimonabant is a cannabinoid receptor type 1 blocker that has been employed in numerous trials involving more than 6,500 patients. It has led to significant weight loss, reduced central fat, and improved glycemic and lipid profiles.

Abdomen↗
PubMed2005

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

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 A1C 6.7 +/- 0.1%), and 11 CC patients (age 35 +/- 3 yr, BMI 25 +/- 1 kg/m2, Hb A1C 9.6 +/- 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 (R(d)) were determined using [3-H3]glucose. Muscle biopsy was performed at the end of each study. IC had a significantly reduced EGP and R(d) responses 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.

Adipose Tissue↗
PubMed2005

Differing physiological effects of epinephrine in type 1 diabetes and nondiabetic humans.

Acute increases of the key counterregulatory hormone epinephrine can be modified by a number of physiological and pathological conditions in type 1 diabetic patients (T1DM). However, it is undecided whether the physiological effects of epinephrine are also reduced in T1DM. Therefore, the aim of this study was to determine whether target organ (liver, muscle, adipose tissue, pancreas, cardiovascular) responses to epinephrine differ between healthy subjects and T1DM patients. Thirty-four age- and weight-matched T1DM (n = 17) and healthy subjects (n = 17) underwent two randomized, single-blind, 2-h hyperinsulinemic euglycemic clamp studies with (Epi) and without epinephrine infusion. Muscle biopsy was performed at the end of each study. Epinephrine levels during Epi were similar in all groups (4,039 +/- 384 pmol/l). Glucose (5.3 +/- 0.06 mmol/l) and insulin levels (462 +/- 18 pmol/l) were also similar in all groups during the glucose clamps. Glucagon responses to Epi were absent in T1DM and significantly reduced compared with healthy subjects. Endogenous glucose production during the final 30 min was significantly greater during Epi in healthy subjects compared with T1DM (8.4 +/- 1.3 vs. 4.4 +/- 0.6 micromol.kg(-1).min(-1), P = 0.041). Glucose uptake showed almost a twofold greater decrease with Epi in healthy subjects vs. T1DM (Delta31 +/- 2 vs. Delta17 +/- 2 nmol.kg(-1).min(-1), respectively, P = 0.026). Glycerol, beta-hydroxybutyrate, and nonesterified fatty acid (NEFA) all increased significantly more in T1DM compared with healthy subjects. Increases in systolic blood pressure were greater in healthy subjects, but reductions of diastolic blood pressure were greater in T1DM patients with Epi. Reduction of glycogen synthase was significantly greater during epinephrine infusion in T1DM vs. healthy subjects. In summary, despite equivalent epinephrine, insulin, and glucose levels, changes in glucose flux, glucagon, and cardiovascular responses were greater in healthy subjects compared with T1DM. However, T1DM patients had greater lipolytic responses (glycerol and NEFA) during Epi. Thus we conclude that there is a spectrum of significant in vivo physiological differences of epinephrine action at the liver, muscle, adipose tissue, pancreas, and cardiovascular system between T1DM and healthy subjects.

Adult↗
PubMed2005

Glucoregulation during and after exercise in health and insulin-dependent diabetes.

An elegant control system prevents hypoglycemia despite dramatic increments in glucose usage by working muscle. Insulin excess disrupts this control system, leading to hypoglycemia. Recent hypoglycemic episodes blunt the glucoregulatory response to subsequent exercise, and exercise blunts the glucoregulatory response to subsequent insulin excess. These mechanisms of glucoregulatory failure may cause hypoglycemia in insulin-dependent diabetics during and after exercise.

Blood Glucose↗
PubMed2004

Brain region-dependent effects of dexamethasone on counterregulatory responses to hypoglycemia in conscious rats.

The aim of this study was to determine whether activation of central type II glucocorticoid receptors can blunt autonomic nervous system counterregulatory responses to subsequent hypoglycemia. Sixty conscious unrestrained Sprague-Dawley rats were studied during 2-day experiments. Day 1 consisted of either two episodes of clamped 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1)) hypoglycemia (2.8 +/- 0.1 mM; n = 12), hyperinsulinemic euglycemia (6.2 +/- 0.1 mM; n = 12), hyperinsulinemic euglycemia plus simultaneous lateral cerebroventricular infusion of saline (24 microl/h; n = 8), or hyperinsulinemic euglycemia plus either lateral cerebral ventricular infusion (n = 8; LV-DEX group), fourth cerebral ventricular (n = 10; 4V-DEX group), or peripheral (n = 10; P-DEX group) infusion of dexamethasone (5 microg/h), a specific type II glucocorticoid receptor analog. For all groups, day 2 consisted of a 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1)) or hypoglycemic (2.9 +/- 0.2 mM) clamp. The hypoglycemic group had blunted epinephrine, glucagon, and endogenous glucose production in response to subsequent hypoglycemia. Consequently, the glucose infusion rate to maintain the glucose levels was significantly greater in this group vs. all other groups. The LV-DEX group did not have blunted counterregulatory responses to subsequent hypoglycemia, but the P-DEX and 4V-DEX groups had significantly lower epinephrine and norepinephrine responses to hypoglycemia compared with all other groups. In summary, peripheral and fourth cerebral ventricular but not lateral cerebral ventricular infusion of dexamethasone led to significant blunting of autonomic counterregulatory responses to subsequent hypoglycemia. These data suggest that prior activation of type II glucocorticoid receptors within the hindbrain plays a major role in blunting autonomic nervous system counterregulatory responses to subsequent hypoglycemia in the conscious rat.

Animals↗
PubMed2004

NO synthase inhibition increases aldosterone in humans.

To test the hypothesis that NO influences aldosterone production in humans, we examined the effect of N(G)-nitro-L-arginine methyl ester (L-NAME) on aldosterone concentrations in the presence and absence of the NO precursor L-arginine (3 g TID) and the angiotensin-converting enzyme inhibitor ramipril (10 mg QD). Ten normal subjects were given L-NAME (66 microg/kg per min for 30 minutes) or vehicle in random order on separate days during placebo and after randomized, double-blind treatment with L-arginine, ramipril, or L-arginine plus ramipril. Infusion of L-NAME significantly increased systolic blood pressure (all P<0.05) and decreased heart rate (all P< or =0.02) during all 4 treatment arms. After placebo pretreatment, serum aldosterone was significantly higher during L-NAME infusion than during vehicle (6.6+/-1.7 versus 3.3+/-0.5 ng/dL; P=0.045). Combined treatment with L-arginine plus ramipril abolished this effect. There was no effect of L-NAME on plasma renin activity (PRA; P=0.297) or angiotensin II concentrations (P=0.537). However, there was a significant interactive effect of L-NAME and time on serum potassium (P=0.039). There was a significant linear relationship between PRA and aldosterone concentration after vehicle infusion ([aldosterone]=3.9.PRA+1.9; r2=0.476; P=0.027) and L-NAME infusion ([aldosterone]=7.2.PRA+3.1; r2=0.457; P=0.032), and the intercepts of these lines were different (P=0.029). There was a significant linear relationship between serum potassium and aldosterone during L-NAME ([aldosterone]=8.2 . [potassium]-28.9; r2=0.609; P=0.008) but not during vehicle (P=0.313). These data suggest that endogenous NO modulates aldosterone synthesis in humans.

Adult↗
PubMed2004

Effect of sex on counterregulatory responses to exercise after antecedent hypoglycemia in type 1 diabetes.

A marked sexual dimorphism exists in healthy individuals in the pattern of blunted neuroendocrine and metabolic responses following antecedent stress. It is unknown whether significant sex-related counterregulatory differences occur during prolonged moderate exercise after antecedent hypoglycemia in type 1 diabetes mellitus (T1DM). Fourteen patients with T1DM (7 women and 7 men) were studied during 90 min of euglycemic exercise at 50% maximal O(2) consumption after two 2-h episodes of previous-day euglycemia (5.0 mmol/l) or hypoglycemia of 2.9 mmol/l. Men and women were matched for age, glycemic control, duration of diabetes, and exercise fitness and had no history or evidence of autonomic neuropathy. Exercise was performed during constant "basal" intravenous infusion of regular insulin (1 U/h) and a 20% dextrose infusion, as needed to maintain euglycemia. Plasma glucose and insulin levels were equivalent in men and women during all exercise and glucose clamp studies. Antecedent hypoglycemia produced a relatively greater (P < 0.05) reduction of glucagon, epinephrine, norepinephrine, growth hormone, and metabolic (glucose kinetics) responses in men compared with women during next-day exercise. After antecedent hypoglycemia, endogenous glucose production (EGP) was significantly reduced in men only, paralleling a reduction in the glucagon-to-insulin ratio and catecholamine responses. In conclusion, a marked sexual dimorphism exists in a wide spectrum of blunted counterregulatory responses to exercise in T1DM after prior hypoglycemia. Key neuroendocrine (glucagon, catecholamines) and metabolic (EGP) homeostatic responses were better preserved during exercise in T1DM women after antecedent hypoglycemia. Preserved counterregulatory responses during exercise in T1DM women may confer greater protection against hypoglycemia than in men with T1DM.

Adaptation, Physiological↗
PubMed2004

The effects of dehydroepiandrosterone sulfate on counterregulatory responses during repeated hypoglycemia in conscious normal rats.

We previously determined that both antecedent hypoglycemia and elevated cortisol levels blunt neuroendocrine and metabolic responses to subsequent hypoglycemia in conscious, unrestrained rats. The adrenal steroid dehydroepiandrosterone sulfate (DHEA-S) has been shown in several studies to oppose corticosteroid action. The purpose of this study was to determine if DHEA-S could preserve counterregulatory responses during repeated hypoglycemia. We studied 40 male Sprague-Dawley rats during a series of 2-day protocols. Day 1 consisted of two 2-h episodes of 1) hyperinsulinemic (30 pmol. kg(-1). min(-1)) euglycemia (6.2 +/- 0.2 mmol/l; n = 12; ANTE EUG), 2) hyperinsulinemic euglycemia (6.0 +/- 0.1 mmol/l; n = 8) plus simultaneous intravenous infusion of DHEA-S (30 mg/kg; ANTE EUG + DHEA-S), 3) hyperinsulinemic hypoglycemia (2.8 +/- 0.1 mmol/l; n = 12; ANTE HYPO), or 4) hyperinsulinemic hypoglycemia (2.8 +/- 0.1 mmol/l; n = 8) with simultaneous intravenous infusion of DHEA-S (30 mg/kg; ANTE HYPO + DHEA-S). Day 2 consisted of a single 2-h hyperinsulinemic hypoglycemic (2.8 +/- 0.1 mmol/l) clamp. During the final 30 min of day 2, hypoglycemia norepinephrine levels were significantly lower in the ANTE HYPO group versus the ANTE HYPO + DHEA-S group (2.0 +/- 0.2 vs. 3.3 +/- 0.6 nmol/l; P < 0.05). In addition, epinephrine (8 +/- 1 vs. 17 +/- 2, 14 +/- 3, and 15 +/- 3 nmol/l), glucagon (91 +/- 8 vs. 273 +/- 36, 231 +/- 42, and 297 +/- 48 ng/l), and corticosterone (1,255 +/- 193 vs. 1,915 +/- 212, 1,557 +/- 112, and 1,668 +/- 119 pmol/l) were significantly lower in the ANTE HYPO group versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (P < 0.05). Endogenous glucose production was also significantly less in the ANTE HYPO group versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (13 +/- 5 vs. 32 +/- 3, 38 +/- 7, and 29 +/- 8 micro mol/l. kg(-1). min(-1); P < 0.05). Consequently, the amount of exogenous glucose needed to maintain the glycemic level during the clamp studies was significantly higher in the ANTE HYPO versus the ANTE EUG, ANTE EUG + DHEA-S, and ANTE HYPO + DHEA-S groups (57 +/- 8 vs. 22 +/- 5, 18 +/- 6, and 18 +/- 3 micro mol/l. kg(-1). min(-1); P < 0.05). In summary, day-1 antecedent hypoglycemia blunted neuroendocrine and metabolic responses to next-day hypoglycemia. However, simultaneous DHEA-S infusion during antecedent hypoglycemia preserved neuroendocrine and metabolic counterregulatory responses during subsequent hypoglycemia in conscious rats.

Animals↗
PubMed2004

Effects of low and moderate antecedent exercise on counterregulatory responses to subsequent hypoglycemia in type 1 diabetes.

Antecedent moderate-intensity exercise has been shown to blunt autonomic, neuroendocrine, and metabolic counterregulatory responses to subsequent hypoglycemia in nondiabetic individuals. The aims of the current study were to determine 1) whether this occurs in type 1 diabetic patients and 2) whether the degree of blunting is dependent on exercise intensity. Twenty-seven type 1 diabetic patients (13 women and 14 men) were studied during a single-step, 2-h hyperinsulinemic (9 pmol x kg(-1) x min(-1))-hypoglycemic (approximately 2.8 mmol/l) clamp 1 day after two 90-min exercise bouts at 30% (n = 11) or at 50% (n = 11) Vo(2max) or after no prior stress (control subjects, n = 25). After prior exercise at both 30 and 50% Vo(2max), epinephrine (1,959 +/- 553 and 1,528 +/- 424 vs. 3,420 +/- 424 pmol/l, respectively; P < 0.05) and pancreatic polypeptide (97 +/- 32 and 98 +/- 8 vs. 223 +/- 32 pmol/l, respectively; P < 0.05) responses to subsequent hypoglycemia were significantly lower compared with those of control subjects. Endogenous glucose production was significantly lower, while glucose utilization and, consequently, the exogenous glucose infusion rate needed to maintain hypoglycemia were significantly greater after both exercise intensities compared with that of control subjects. Muscle sympathetic nerve activity was significantly reduced by prior exercise of both intensities at baseline (16 +/- 4 and 22 +/- 4 vs. 31 +/- 3 bursts/min) and during hypoglycemia (22 +/- 4 and 27 +/- 5 vs. 41 +/- 3 bursts/min) compared with that of control subjects (P < 0.05). Total hypoglycemic symptoms were also significantly lower (P < 0.05) in both exercise groups compared with the control group. In summary, repeated episodes of prolonged exercise of both low and moderate intensities blunted key autonomic (epinephrine and pancreatic polypeptide) and metabolic (endogenous glucose production and peripheral glucose uptake) counterregulatory responses to next-day hypoglycemia in type 1 diabetes.

Adult↗
PubMed2004

Optimizing combination therapy for type 2 diabetes in adolescents and adults: a case-based approach.

Children and adolescents who are overweight and have additional risk factors (ie, high-risk ethnic group or signs of insulin resistance) should be screened for diabetes every 2 years (strength of recommendation [SOR]: C). Management of type 2 diabetes in all age groups requires a multifactorial approach that addresses not only glycemic control (A1C <7%) but also other cardiovascular risk factors such as hypertension, dyslipidemia, and obesity (SOR: A). Most patients with type 2 diabetes will eventually require combination therapy with 2 or more agents to attain and maintain glycemic control (SOR: A). Combining an insulin secretagogue (ie, sulfonylurea or meglitinide) and an insulin sensitizer (ie, metformin or a glitazone) capitalizes on unique mechanisms of action and results in significant A1C lowering (SOR: C). If a patient is unable to achieve glycemic control on 2 oral agents, insulin therapy is an appropriate consideration and should be added to oral agents (rather than substituted) (SOR: B).

Administration, Oral↗