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Biomedical subjects

W Renn

Publications and source records attributed to W Renn.

At least 37 records · Page 2Linked to original sources
PubMed1999

Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; however, the multiple mechanisms causing insulin resistance are not yet fully understood. The aim of this study was to explore the possible contribution of intramyocellular lipid content in the pathogenesis of skeletal muscle insulin resistance. We compared insulin-resistant and insulin-sensitive subjects. To meet stringent matching criteria for other known confounders of insulin resistance, these individuals were selected from an extensively metabolically characterized group of 280 first-degree relatives of type 2 diabetic subjects. Some 13 lean insulin-resistant and 13 lean insulin-sensitive subjects were matched for sex, age, BMI, percent body fat, physical fitness, and waist-to-hip ratio. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic clamp method (for insulin-resistant subjects, glucose metabolic clearance rate [MCR] was 5.77+/-0.28 ml x kg(-1) x min(-1) [mean +/- SE]; for insulin-sensitive subjects, MCR was 10.15+/-0.7 ml x kg(-1) x min(-1); P<0.002). Proton magnetic resonance spectroscopy (MRS) was used to measure intramyocellular lipid content (IMCL) in both groups. MRS studies demonstrated that in soleus muscle, IMCL was increased by 84% (11.8+/-1.6 vs. 6.4+/-0.59 arbitrary units; P = 0.008 ), and in tibialis anterior muscle, IMCL was increased by 57% (3.26+/-0.36 vs. 2.08+/-0.3 arbitrary units; P = 0.017) in the insulin-resistant offspring, whereas the extramyocellular lipid content and total muscle lipid content were not statistically different between the two groups. These data demonstrate that in these well-matched groups of lean subjects, IMCL is increased in insulin-resistant offspring of type 2 diabetic subjects when compared with an insulin-sensitive group matched for age, BMI, body fat distribution, percent body fat, and degree of physical fitness. These results indicate that increased IMCL represents an early abnormality in the pathogenesis of insulin resistance and suggest that increased IMCL may contribute to the defective glucose uptake in skeletal muscle in insulin-resistant subjects.

Adult↗
PubMed1998

Diabetes teaching program improves glycemic control and preserves perception of hypoglycemia.

Improvement of HbA1c is frequently accompanied by deteriorating awareness of hypoglycemia. We studied the effect of improved metabolic control on hypoglycemia perception in 33 type 1 diabetic patients during 3 months after an inpatient diabetes education program of 5 days. Patients were grouped according to the presence (H, n = 11) or the absence (N, n = 22) of a history of repeated severe hypoglycemia. To measure awareness of blood glucose (BG) and hypoglycemia, we calculated their accuracy of BG perception (error grid analysis) and sensitivity for BG levels < 3.9 mmol/l, respectively, during the first (I) and second (II) period of the 3 months using the method of BG estimation. HbA1c decreased from 8.0 +/- 0.3% before to 7.1 +/- 0.2% 3 months after the program (P < 0.001) with no difference between H and N. Neither accuracy of BG perception (40.6 +/- 3.8 (I) versus 43.6 +/- 4.1% (II), P = 0.25) nor sensitivity for low BG levels (49.1 +/- 4.2 (I) versus 54.9 +/- 4.9% (II), P = 0.12) changed significantly. Group H had a lower overall accuracy of BG estimation (P = 0.048) and a lower overall sensitivity for detecting BG levels < 3.9 mmol/l (P = 0.03) than group N. Group H was able to improve accuracy of BG estimation (H: 24.8 +/- 6.2 (I) versus 36.9 +/- 8.3% (II), P = 0.04) while group N was not (48.5 +/- 3.9 (I) versus 46.9 +/- 4.6% (II), P = 0.5). In conclusion, improvement of metabolic control after intensive diabetes education had no adverse effect on the perception of low BG levels. On the contrary, patients with a history of severe hypoglycemia improved their awareness of BG.

Adult↗
PubMed1998

Evidence for inhibition of leptin secretion by catecholamines in man.

The regulation of leptin secretion is complex and not entirely understood in humans. Insulin has been shown to stimulate leptin secretion in humans, whereas in vitro data suggest that catecholamines inhibit leptin secretion. The present studies were therefore undertaken to examine the leptin response to hyperinsulinemia in the presence and absence of elevated plasma levels of endogenous catecholamines in humans. Leptin concentrations were determined during both a euglycemic and hypoglycemic hyperinsulinemic clamp study in 10 normal and 10 type I diabetic subjects. Serum leptin increased during the hyperinsulinemic euglycemic clamp in normal (from 6.1 +/- 0.9 to 7.2 +/- 1.1 ng/dl, p = 0.003) and diabetic subjects (from 6.2 +/- 1.4 to 7.8 +/- 1.8 ng/dl, p = 0.001). During hyperinsulinemic hypoglycemia leptin concentrations increased significantly in type 1 diabetic patients (from 5.6 +/- 1.1 to 7.6 +/- 1.7 ng/dl, p = 0.003) but remained unaltered in normals (from 5.5 +/- 0.7 to 5.7 +/- 0.9 ng/dl, p = 0.7). During hypoglycemia in all subjects the increase in leptin was negatively correlated with the increase in epinephrine (r = 0.60, p = 0.005) and positively with the decrease in free fatty acids (r = 0.71, p = 0.003). In conclusion our results indicate that catecholamines play a suppressive role in the regulation of leptin secretion.

Adult↗
PubMed1998

Parathyroid hormone after adenectomy for primary hyperparathyroidism. A study of peptide hormone elimination kinetics in humans.

The study of the elimination kinetics of peptide hormones in humans is limited, because determining hormone levels in different compartments is difficult. We calculated the elimination kinetics of intact PTH (1-84) after adenoma removal in primary hyperparathyroidism, based on a 2-compartment model. In 12 patients, blood samples were drawn in short intervals preoperatively, during surgery, and up to 4 days postoperatively. Plasma levels of PTH (1-84), calcium (Ca), and inorganic phosphate were determined. PTH (1-84) levels remained constant before surgery and during adenoma preparation; 2.5 min after clamping of the adenoma's blood supply, PTH (1-84) decreased (34.9 +/- 4.8 vs. 23.3 +/- 2.9 pmol/L, mean +/- SEM, P < 0.001) and then reached a minimum of 0.96 +/- 0.06 pmol/L at 5 h. The elimination half-lives for PTH (1-84) were 3.43 +/- 0.1 min and 81.7 +/- 12.7 min. Ionized Ca started to decrease 30 min after adenoma removal (1.58 +/- 0.04 vs. 1.56 +/- 0.04 pmol/L, P < 0.001). This decrease was paralleled by a decrease in total Ca. Inorganic phosphate increased 24 h after adenoma removal. In conclusion, PTH (1-84) elimination after adenectomy is characterized by a rapid initial decrease and a subsequent prolonged period with a lower elimination rate. This elimination pattern may also apply to other human peptide hormones.

Adenoma↗
PubMed1998

Effect of hypoglycemia on beta-adrenergic sensitivity in normal and type 1 diabetic subjects.

OBJECTIVE: The purpose of this study was to assess the potential role of reduced tissue sensitivity to catecholamines in the pathogenesis of hypoglycemia unawareness in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: The effect of a single episode of hypoglycemia on beta-adrenergic sensitivity was studied in 10 type 1 diabetic patients with apparently normal awareness of hypoglycemia (age 29 +/- 5 years, diabetes duration 13 +/- 8 years, HbA1c 7.3 +/- 0.9%) and 10 age-matched healthy control subjects. Beta-adrenergic sensitivity was measured with the isoproterenol test after a hyperinsulinemic euglycemic clamp and after a hyperinsulinemic hypoglycemic clamp. Beta-adrenergic sensitivity was expressed as the dose of intravenous isoproterenol that increased the heart rate by 25 beats/min (IC25). RESULTS: During hypoglycemia, diabetic subjects had an impaired plasma epinephrine response compared with that of the control subjects (16.7 +/- 5.0 vs. 40.1 +/- 6.8 ng/ml, P = 0.02). In control subjects, the IC25 was lower after hypoglycemia than after euglycemia (0.83 +/- 0.22 vs. 1.13 +/- 0.21 microg, P = 0.02) indicating an increase in beta-adrenergic sensitivity. In diabetic subjects, on the other hand, the IC25 was greater after hypoglycemia than after euglycemia (1.00 +/- 0.26 vs. 0.65 +/- 0.14 microg, P = 0.04), indicating a decrease in beta-adrenergic sensitivity. CONCLUSIONS: In normal subjects, a single episode of hypoglycemia increases beta-adrenergic sensitivity. In diabetic subjects, in contrast, hypoglycemia reduces beta-adrenergic sensitivity. These results provide evidence that in type 1 diabetic patients, some maladaptation of tissue sensitivity to catecholamines contributes to the development of hypoglycemia unawareness. A unifying hypothesis is presented for the pathogenesis of hypoglycemia unawareness in type 1 diabetic patients incorporating the concepts of both a reduced catecholamine response and reduced adrenergic sensitivity

Adrenergic beta-Agonists↗
PubMed1997

Perfusion-independent effect of bradykinin and fosinoprilate on glucose transport in Langendorff rat hearts.

Angiotensin-converting enzyme (ACE) inhibitor-stimulated glucose metabolism and perfusion in muscle tissue seem to be, at least in part, mediated by kinins. However, the relative contribution of direct metabolic or secondary hemodynamically induced effects is unclear. It was the aim of this study to characterize the effects of ACE inhibition and bradykinin on glucose transport while changes in cardiocoronary function that might influence glucose transport were minimized. Hearts from Wistar rats were perfused by a Langendorff preparation and a set of functional parameters were simultaneously measured. Bradykinin (10[-11] M) and fosinoprilate (10[-7] M) were administered at concentrations that did not affect coronary flow. Insulin was employed as reference at half-maximal concentration. The nonmetabolizable glucose analog 3-O-[14C]methyl-D-glucose and the nontransportable tracer L-[3H]glucose were coperfused for the calculation of glucose transport. Using a 2-compartment mathematical model we found that the glucose transport rate, which was doubled with insulin, was increased almost 3-fold by either bradykinin or fosinoprilate. In the presence of the B2 bradykinin receptor antagonist HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin; icatibant), the effect of both agents was completely abolished. Both agents also induced minor changes in contractility/relaxation parameters that again were completely neutralized with icatibant. A perfusion-independent but B2-kinin receptor-dependent stimulating effect on glucose transport by either bradykinin or fosinoprilate is concluded. This effect could, in analogy to insulin be due to increased glucose transporter translocation, increased endothelium-derived nitric oxide formation, or--despite constant coronary flow conditions--secondary to altered cardiac function.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Glucose turnover in humans in the basal state and after intravenous glucose: a comparison of two models.

This study investigated the ability of two models to represent glucose kinetics in the basal steady state and during an intravenous glucose tolerance test (IVGTT). Six young nonobese male subjects were studied after an overnight fast. Two bolus injections of [U-13C]glucose were given 150 min apart, the first without and the second together with concomitant injection of unlabeled glucose. [3-3H]glucose was constantly infused throughout the study and served to provide an independent means for evaluation of system responses. A linear time-invariant three-compartmental model and the two-compartment time-variant model proposed by Caumo and Cobelli were used to interpret measured time courses of [U-13C]glucose and to reconstruct endogenous glucose production and glucose removal. The ability of the two models to describe the glucose tracer time course was comparable. Simulation studies showed that the two-compartmental time-variant system better predicted measured [3-3H]glucose concentration profiles than did the three-compartmental time-invariant model. However, endogenous glucose production and the integral of excess glucose removal over basal during the IVGTT derived from the two models were almost identical.

Adult↗
PubMed1996

Circulating TNF-alpha and leptin levels in offspring of NIDDM patients do not correlate to individual insulin sensitivity.

Obesity plays a central role in the development of skeletal muscle insulin resistance. The molecular mechanism causing skeletal muscle insulin resistance in obese people is still poorly understood. It has been speculated that circulating factors derived from adipose tissue impair insulin signalling in the skeletal muscle cell. TNF-alpha and leptin, which are overproduced in fat tissue of obese insulin resistant animal models and in obese humans, might mediate such an inhibitory effect on insulin signalling in skeletal muscle. The aim of the present study was to evaluate whether circulating TNF-alpha and leptin correlates to the individual skeletal muscle insulin sensitivity in individuals with different degrees of obesity and insulin resistance. We measured circulating TNF-alpha and leptin values in non diabetic offsprings of NIDDM patients. 36 German and 47 Finnish subjects participated in the study. The GDR of each participant was determined by the euglycemic hyperinsulinemic clamp technique, a range between 1.37 to 14.01 mg/kg LBM x min was observed. Percent of desirable body weight (PDW) covered also a wide range (87.58% to 197.06%). Although linear regression analysis suggested a dependence between TNF-alpha and GDR (Germany group: r = -0.37, p < 0.05, Finnish group: r = -0.32, p < 0.05) and a dependence between TNF and PDW (German group: r = 0.46, p < 0.05, Finnish group: r = 0.38, p < 0.05), in multiple linear regression analysis only the correlation with PDW was significant. Leptin levels were measured from 29 German and 36 Finnish subjects and a strong association was found between leptin and PDW (German group: r = 0.55, p < 0.05, Finnish group: r = 0.73, p < 0.05). In contrast, leptin levels did not correlate with GDR and TNF-alpha. In summary, even though, in a few insulin resistant subjects, higher circulating TNF-alpha or leptin levels with the individual insulin sensitivity can be demonstrated, the data suggest that the circulating pool of TNF-alpha and leptin in blood is unlikely to be a major contributing factor for obesity induced insulin resistance in the vast majority of individuals at high risk to develop NIDDM.

Adult↗
PubMed1996

Insulin-associated modulation of neuroendocrine counterregulation, hypoglycemia perception, and cerebral function in insulin-dependent diabetes mellitus: evidence for an intrinsic effect of insulin on the central nervous system.

Evidence for an intrinsic effect of insulin on the central nervous system is accumulating. To test the hypothesis that insulin per se may modulate neuroendocrine counterregulation, hypoglycemia perception, and cerebral function in insulin-dependent diabetes mellitus, we examined 27 patients without any sign of classical autonomic neuropathy or evidence of so-called hypoglycemia unawareness. We used the hyperinsulinemic (0.67 vs. 2.00 mU/kg.min), stepped hypoglycemic (5.6/3.5/2.4/2.0 mmol/L) clamp technique to assess the patient's awareness of and response to equivalent hypoglycemic stimuli under different degrees of physiological hyperinsulinemia (approximately 270 vs. approximately 810 pmol/L) after an overnight euglycemic clamp (5.6 mmol/L). Simultaneously, the patient's cerebral function was assessed from his electrophysiological activity and neuropsychological skills. Higher degrees of physiological hyperinsulinemia caused enhanced neuroendocrine response (adrenaline, P < 0.05; noradrenaline, P < 0.03; GH, P < 0.02; beta-endorphin, P < 0.03; ACTH, P = 0.12; cortisol, P = 0.06; PRL, P = 0.08) and symptom awareness (total symptoms, P < 0.04; autonomic symptoms, P < 0.02; neuroglycopenia symptoms, P < 0.05; sweating, P < 0.05; heart pounding, P < 0.02; trembling, P < 0.01; lack of concentration, P < 0.02) to occur. Deteriorations of electrophysiological activity (middle latency auditory-evoked potentials, P < 0.04; Pa peak latencies, P < 0.05; Pa-V interpeak latencies, P = 0.08) and neuropsychological skills (Stroop test, P < 0.05; trail making, P = 0.12) were more pronounced the higher the insulin level, but at similar blood glucose concentrations. We conclude that insulin-associated modulation of neuroendocrine counterregulation, hypoglycemia perception, and cerebral function may occur in insulin-dependent diabetes mellitus, which indicates an intrinsic effect of insulin on the human brain.

Adult↗
PubMed1996

Pain intensity and blood pressure reactions during a cold pressor test in IDDM patients.

OBJECTIVE: To determine the contribution of altered pain perception to the impaired blood pressure reactions during a cold pressor test in diabetic patients. Reduced blood pressure increases have been observed in diabetic patients during a cold pressor test and have been attributed to an impaired efferent sympathetic function. RESEARCH DESIGN AND METHODS: We investigated pain intensities and blood pressure reactions simultaneously during a cold pressor test in 30 IDDM patients (diabetes duration 12 +/- 6 years, HbA1c 7.5 +/- 1.4%) and in 30 normal control subjects with comparable sex distribution, age, height, BMI, physical fitness, and smoking habits. RESULTS: Initial pain intensities and respective time courses did not differ between the two groups. The initial blood pressure response was significantly smaller in diabetic patients (P < 0.002). Correlations of diastolic blood pressure increases in diabetic patients with initial pain intensity, standard cardiovascular reflex tests, age, clock time, smoking habits, disease duration, and actual blood glucose concentrations did not reach statistical significance. Pain intensity and diastolic blood pressure increases, however, were correlated to HbA1c concentrations in diabetic patients. CONCLUSIONS: Impaired pain perception is not the cause of the impaired reactions of blood pressure in diabetic patients during the cold pressor test, leaving very early deterioration of either cerebral processing of pain stimuli, cardiac function, efferent sympathetic nerves, or decreased vascular reactivity as possible explanations.

Adult↗
PubMed1995

Improvement of impaired counterregulatory hormone response and symptom perception by short-term avoidance of hypoglycemia in IDDM.

OBJECTIVE: To test the hypothesis that impaired counterregulatory hormone response and symptom perception, induced by recurrent hypoglycemic episodes over 2 days, may be improved by short-term (2-day) avoidance of hypoglycemia. RESEARCH AND DESIGN: We examined two groups of insulin-dependent diabetes mellitus (IDDM) patients (n = 16), none of whom exhibited signs of peripheral or autonomic neuropathy. Two sequential euglycemic-hypoglycemic clamp studies were performed applying stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l, at which the patients' awareness of and responses to hypoglycemia were evaluated. In the intervention group (n = 11), three short-term hypoglycemic ( < 2.2 mmol/l) episodes (days 1-3) preceded the first clamp study (day 4), whereas the second clamp study (day 6) followed a 2-day interval of strict avoidance of hypoglycemia. A control group (n = 5) was introduced to detect adaptation effects caused by the study procedure per se. RESULTS: This short-term avoidance of hypoglycemia caused improvement of the impaired counterregulatory hormone response during insulin-induced hypoglycemia involving adrenaline (P < 0.05), adrenocorticotrophic hormone (P < 0.03), and cortisol (P < 0.05). Improvement of hypoglycemia symptom awareness encompassed overall symptom perception (multiple analysis of variance, P < 0.04) and the automatic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05). CONCLUSIONS: The previously reported compromised neuroendocrine counterregulation and symptom awareness, occurring as a consequence of repetitive hypoglycemic episodes over 2 days, may be improved by a single 2-day interval of strict avoidance of hypoglycemia

Adult↗
PubMed1994

Differential diagnosis of neuropathic lesions in diabetic and alcoholic patients.

Cardiovascular reflex tests are used extensively to screen diabetic patients for autonomic cardiac neuropathy. Since alcohol abuse must often be considered the cause of nerve damage in internally ill patients, we examined 66 nonalcoholic type 1 (insulin-dependent) diabetics and 63 nondiabetic alcoholics matched for age, weight, and duration of disease to determine whether specific patterns of complaints, symptoms, signs, and results of the cardiovascular reflex tests can differentiate between alcoholic and diabetic nerve damages. In these carefully selected diabetic and alcoholic patients the medical history, clinical neurological assessment, and reflex test results all showed significant differences, resulting in different patterns which allow the correct allocation of nerve damage to either diabetic or alcoholic origin with easily available clinical means.

Adolescent↗
PubMed1994

Recovery of hypoglycaemia-associated compromised cerebral function after a short interval of euglycaemia in insulin-dependent diabetic patients.

To test the hypothesis that compromised cerebral function, induced by recurrent hypoglycaemic episodes, may recover after a short interval of euglycaemia, we examined electrophysiological activity and symptom awareness during two sequential euglycaemic-hypoglycaemic clamp studies in 11 insulin-dependent diabetic patients without any signs of peripheral or autonomic neuropathy. Neurophysiological testing and evaluation of hypoglycaemic symptoms were performed at stable glycaemic plateaus of 5.6, 3.3, 2.2, and 1.7 mmol/l. The first clamp study was preceded by 3 short-term hypoglycaemic episodes, whereas the second clamp study followed a 2 day interval of strict euglycaemia. The latter caused a recovery of electrophysiological activity, which was demonstrated by recovery of delays of the middle latency auditory evoked potentials (latency shift of the P(a) component, MANOVA, P < 0.01). Reversal of hypoglycaemic symptom unawareness involved the overall symptom perception (MANOVA, P < 0.04), as well as the autonomic symptoms of heart pounding (P < 0.05) and sweating (P < 0.05). We conclude that the previously reported impaired cerebral function, occurring as a consequence of repetitive hypoglycaemic episodes, may recover after a single euglycaemic interval.

Acoustic Stimulation↗
PubMed1994

Recovery of the hypothalamic-pituitary-adrenal axis from suppression by short-term, high-dose intravenous prednisolone therapy in patients with MS.

We have studied the recovery of the hypothalamic-pituitary-adrenal (HPA) axis from inhibition by short-term, intravenous high-dose, corticosteroid therapy (IVHDCT) without subsequent oral replacement therapy in 10 patients with relapsing-remitting or progressive multiple sclerosis (MS) using the human corticotrophin-releasing hormone (hCRH) test. There was significant HPA suppression with profoundly decreased basal and peak plasma ACTH and cortisol levels 24 h after cessation of therapy. However, at 48 h the pituitary response was greatly enhanced with peak ACTH concentrations rising by more than 100% over baseline values in 7 of 10 patients. Basal and stimulated ACTH concentrations returned to pre-treatment levels at 120 h. Basal and stimulated plasma cortisol levels remained subnormal in 6 patients 120 h after IVHDCT. We conclude that IVHDCT without oral replacement therapy in MS patients is endocrinologically safe.

Adrenocorticotropic Hormone↗
PubMed1993

Hypothalamic-pituitary activation does not differ during human and porcine insulin-induced hypoglycemia in insulin-dependent diabetes mellitus.

Although pituitary hormones play only a minor role in acute hormonal counterregulation during insulin-induced hypoglycemia, their concomitant secretion with the profound sympathoadrenal response provides an indicator of hypothalamic-pituitary activation. The release of different amounts of beta-endorphin, growth hormone, and adrenocorticotropin during human (HI) and porcine (PI) insulin-induced hypoglycemia would serve as a pointer to a different insulin species effect on hypothalamic-pituitary response. We performed a controlled, double-blind study with randomization to either HI or PI to compare insulin effects during developing and established hypoglycemia. The glucose clamp technique was used to lower the blood glucose concentration stepwise (3.3, 2.2, 1.7 mmol/l) over similar periods in ten patients with insulin-dependent diabetes mellitus. beta-endorphin, growth hormone, and adrenocorticotropin levels were determined by radioimmunoassay from arterialized blood at the above plateaus. A different action of HI or PI on peripheral glucose metabolism was not found. Pituitary hormones increased significantly during hypoglycemia (analysis of variance for hypoglycemic effects: beta-endorphin, P < 0.02; growth hormone, P < 0.04; adrenocorticotropin, P < 0.05). No insulin species effect was detected. Hypothalamic-pituitary activation during insulin-induced hypoglycemia is independent of the insulin species used, which supports earlier observations of an identical sympathoadrenal response during HI- and PI-induced hypoglycemia.

Adrenocorticotropic Hormone↗
PubMed1993

Compromised hormonal counterregulation, symptom awareness, and neurophysiological function after recurrent short-term episodes of insulin-induced hypoglycemia in IDDM patients.

To test the hypothesis that recurrent short-term hypoglycemic episodes may impair hormonal counterregulation, symptom awareness, and neurophysiological function during subsequent hypoglycemia, we examined two groups of IDDM patients (n = 18), neither of whom exhibited signs of autonomic neuropathy. Two sequential euglycemic-hypoglycemic clamp studies were performed three days apart with stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM, at which the patients' awareness of and response to hypoglycemia was evaluated. In the intervention group (n = 11), three short-term hypoglycemic episodes preceded the second clamp study. Counterregulatory hormones increased significantly during hypoglycemia, but adrenaline (P < 0.03), cortisol (P < 0.01), and ACTH (albeit not significant) showed a blunted response after repetitive hypoglycemic events. In this group, the perception of hypoglycemic symptoms was significantly reduced and was most evident for the autonomic symptoms of sweating (P < 0.05), heart pounding (P < 0.01), and warmness (P < 0.03). The deterioration of neurophysiological function, as assessed from the middle latency auditory evoked potentials, was more pronounced in the intervention group (latency shift of the Pa component, P < 0.05). These data suggest that alterations of neuroendocrine counterregulation, symptom perception, and certain aspects of cerebral function may occur as a consequence of recurrent short-term hypoglycemic episodes. These adaptation phenomena may contribute to the increased incidence of severe hypoglycemia in IDDM patients on intensive insulin therapy.

Adrenocorticotropic Hormone↗
PubMed1993

Neurophysiological impairments in IDDM patients during euglycemia and hypoglycemia.

OBJECTIVE: To test the hypothesis that latencies of evoked potentials in IDDM patients are delayed compared with healthy control subjects during euglycemia, and that insulin-induced hypoglycemia causes further latency delays of evoked potentials to occur. RESEARCH DESIGN AND METHODS: We recruited 23 IDDM patients (27.9 +/- 1.6 yr of age, HbA1c 6.7 +/- 0.3%, without sensory or autonomic neuropathy) and 26 unequivocally healthy subjects who were carefully matched for sex, age, and body mass index to serve as the control group (18 men and 8 women, 28.4 +/- 1.6 yr of age, 22.6 +/- 0.7 kg/m2), for a controlled, prospective study. Sequential euglycemic-hypoglycemic clamps were performed with stable glycemic plateaus of 5.6, 3.3, 2.2, and 1.7 mM, at which the patients' and healthy control subjects' neurophysiological functions were evaluated. The methodological armamentarium included the measurement of brainstem auditory, middle-latency auditory, and somatosensory evoked potentials that assessed conduction velocity in corresponding neural structures and information processing in the midbrain and auditory cortex. RESULTS: Multiple analysis of variance revealed a significant overall difference of brainstem auditory evoked potential latencies during euglycemia between the study group and healthy control group (F = 3.41, P < 0.03), which was mainly attributable to latency delays of wave III (F = 6.60, P < 0.02), V (F = 9.19, P < 0.01), and interpeak latency I-V (F = 2.82, P < 0.07). Repeated analysis of variance measures detected a significant latency delay of the major wave Pa of the middle-latency auditory evoked potentials during hypoglycemia (F = 4.4, P < 0.02), which rapidly returned to normal after reinstitution of euglycemia. CONCLUSIONS: In IDDM patients, chronic, structural CNS changes already appear at the brainstem level during euglycemia. Functional, reversible CNS changes, however, seem to emerge during acute deviation from glucose homeostasis in more rostral brain regions.

Adult↗