Counterregulatory Hormone Secretion Research Articles

Coefficient of variation of R-R interval closely correlates with glycemic variability assessed by continuous glucose monitoring in insulin-depleted patients with type 1 diabetes

AimsIn type 1 diabetic patients, insulin secretory capacity, meals and physical activity correlate with glycemic variability. Autonomic function associated with gastrointestinal motility and counterregulatory hormone secretion is another candidate which correlates with glucose variability. The aim of this study is to clarify a new clinical parameter associated with glycemic variability in insulin-depleted patients with type 1 diabetes. MethodsWe studied 31 inpatients with type 1 diabetes. We evaluated glycemic variability calculated by continuous glucose monitoring, clinical parameters and the coefficient of variation of R-R interval (CVR-R). Glycemic variability was also assessed during the daytime and nighttime. ResultsThe CVR-R showed a significant negative correlation with the whole-day standard deviation (SD) (r=−0.50, p=0.007), mean amplitude of glycemic excursions (MAGE) (r=−0.47, p=0.011), M-value (r=−0.38, p=0.048) and mean of daily differences (MODD) (r=−0.59, p=0.001). The CVR-R also showed a significant negative correlation with the nighttime SD (r=−0.59, p=0.001), MAGE (r=−0.47, p=0.011), M-value (r=−0.53, p=0.004) and MODD (r=−0.65, p=0.0003). And furthermore, the CVR-R also showed a significant negative correlation with the daytime SD (r=−0.44, p=0.019) and MAGE (r=−0.50, p=0.006), but not with the daytime M-value or MODD. The nighttime SD was significantly higher in patients with diabetic polyneuropathy than in patients without it (p=0.016), while the CVR-R was significantly lower in patients with polyneuropathy than in patients without it (p=0.009). ConclusionsCVR-R is closely correlated with glycemic variability, especially during nighttime, in insulin-depleted patients with type 1 diabetes. Measuring CVR-R may help us to presume the degree of glycemic variability in those patients.

Neural regulation of pancreatic islet cell mass and function.

Intracellular glucose signalling pathways control the secretion of glucagon and insulin by pancreatic islet α- and β-cells, respectively. However, glucose also indirectly controls the secretion of these hormones through regulation of the autonomic nervous system that richly innervates this endocrine organ. Both parasympathetic and sympathetic nervous systems also impact endocrine pancreas postnatal development and plasticity in adult animals. Defects in these autonomic regulations impair β-cell mass expansion during the weaning period and β-cell mass adaptation in adult life. Both branches of the autonomic nervous system also regulate glucagon secretion. In type 2 diabetes, impaired glucose-dependent autonomic activity causes the loss of cephalic and first phases of insulin secretion, and impaired suppression of glucagon secretion in the postabsorptive phase; in diabetic patients treated with insulin, it causes a progressive failure of hypoglycaemia to trigger the secretion of glucagon and other counterregulatory hormones. Therefore, identification of the glucose-sensing cells that control the autonomic innervation of the endocrine pancreatic and insulin and glucagon secretion is an important goal of research. This is required for a better understanding of the physiological control of glucose homeostasis and its deregulation in diabetes. This review will discuss recent advances in this field of investigation.

The Case for: Hypoglycemia Is of Cardiovascular Importance

Hypoglycemia, defined as a plasma glucose concentration <70 mg/dL, represents a major and potentially very dangerous side effect of glucose-lowering therapies in patients with diabetes, and it challenges the patient’s ability to achieve and maintain optimal glycemic control (1–3). Statistically, the incidence of mild hypoglycemia in patients with type 1 diabetes is ~30 episodes/patient/year, whereas the incidence of severe hypoglycemia (i.e., requiring third-party assistance) may be as high as 3.2 episodes/patient/year (4). Furthermore, an estimated 2–4% of deaths of people with type 1 diabetes have been attributed to hypoglycemia. On the other hand, patients with type 2 diabetes experience hypoglycemia less frequently, with an incidence of mild and severe hypoglycemic episodes of 2–10/patient/year and 0.1–0.7/patient/year, respectively (4). The occurrence of hypoglycemia, both in experimental and human settings even without diabetes or related metabolic changes, provokes substantial increase in counterregulatory hormonal secretion and affects the cardiovascular system and the brain, in turn affecting cognition, mood, and the level of consciousness. The secretion of counterregulatory hormones—of which glucagon and epinephrine are the most potent but also including norepinephrine, vasopressin, growth hormone, and cortisol—follows suppression of endogenous insulin secretion (5). In addition, a specific response that occurs within the brain includes the activation of the central sympathetic nervous system, which promotes autonomic symptoms such as sweating, tremor, a pounding heart, hunger, and anxiety (6). Severe hypoglycemia is associated with significant morbidity such as cognitive impairment and can cause major neurological disability, including difficulty concentrating, drowsiness, and poor coordination. When blood glucose falls below 2.8 mmol/L, the majority of cognitive modalities are impaired. It is essential for a patient to be aware of these neuroglycopenic symptoms because they warn him/her that prompt action is required to treat the hypoglycemia and restore blood glucose to normal. In rare cases, prolonged severe …

Caudal fourth ventricular administration of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside regulates glucose and counterregulatory hormone profiles, dorsal vagal complex metabolosensory neuron function, and hypothalamic fos expression

This study investigated the hypothesis that estrogen controls hindbrain AMP-activated protein kinase (AMPK) activity and regulation of blood glucose, counterregulatory hormone secretion, and hypothalamic nerve cell transcriptional status. Dorsal vagal complex A2 noradrenergic neurons were laser microdissected from estradiol benzoate (E)- or oil (O)-implanted ovariectomized female rats after caudal fourth ventricular (CV4) delivery of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR), for Western blot analysis. E advanced AICAR-induced increases in A2 phospho-AMPK (pAMPK) expression and in blood glucose levels and was required for augmentation of Fos, estrogen receptor-α (ERα), monocarboxylate transporter-2, and glucose transporter-3 protein in A2 neurons and enhancement of corticosterone secretion by this treatment paradigm. CV4 AICAR also resulted in site-specific modifications in Fos immunolabeling of hypothalamic metabolic structures, including the paraventricular, ventromedial, and arcuate nuclei. The current studies demonstrate that estrogen regulates AMPK activation in caudal hindbrain A2 noradrenergic neurons during pharmacological replication of energy shortage in this area of the brain, and that this sensor is involved in neural regulation of glucostasis, in part, through control of corticosterone secretion. The data provide unique evidence that A2 neurons express both ERα and -β proteins and that AMPK upregulates cellular sensitivity to ERα-mediated signaling during simulated energy insufficiency. The results also imply that estrogen promotes glucose and lactate uptake by these cells under those conditions. Evidence for correlation between hindbrain AMPK and hypothalamic nerve cell genomic activation provides novel proof for functional connectivity between this hindbrain sensor and higher order metabolic brain loci while demonstrating a modulatory role for estrogen in this interaction.

In-hospital Management of Diabetes

In-hospital Management of Diabetes

In-Hospital Management of Diabetes.

In-Hospital Management of Diabetes.

Effects of Sleep Restriction on Glucose Control and Insulin Secretion During Diet‐Induced Weight Loss

Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-hour blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean [SD] age 41 [5] y; BMI 27.4 [2.0] kg/m2) completed two 14-day treatments with hypocaloric diet and 8.5 or 5.5-h nighttime sleep opportunity in random order 7 [3] months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free-fatty acids (FFA), and 24-hour blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 [0.3] BMI units) during each treatment. Bedtime restriction reduced sleep by 131 [30] min/day. Recurrent sleep curtailment decreased 24-hour serum insulin concentrations (i.e. enhanced 24-hour insulin economy) without changes in oral glucose tolerance and 24-hour glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA which suppressed normally following glucose ingestion, and lower total and LDL cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-hour insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability.

Diabetes in the Competitive Athlete

Diabetes mellitus is the most common group of metabolic diseases and is characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Most patients with diabetes are type 2 (90%); the remaining patients have type 1 disease. Athletes with diabetes range from the athlete participating in various youth sports to the competitive Olympic athlete and present a significant challenge to themselves and the medical staff who care for them on a daily basis. Each sport and the type of exercise have their own effects on diabetes management with numerous factors that significantly affect glucose levels, including stress, level of hydration, the rate of glycogenolysis and gluconeogenesis, and the secretion of counter-regulatory hormones. This article provides a general overview of diabetes mellitus, the effects of exercise on glucose levels, and a detailed review of the potential complications encountered in the management of diabetes in the athlete.

Closing the Loop: Another Step Forward

To achieve normoglycemia in people with diabetes, the complex hormonal and neuronal influences that regulate glucose homeostasis must be understood and addressed. In addition to insulin deficiency, abnormalities include dysregulation in the secretion and/or action of glucagon, incretins, and other counterregulatory hormones. Efforts to restore normal metabolism in diabetes with insulin therapy alone have been suboptimal, with hypoglycemia being a major problem. Pancreatic transplantation is restricted by the availability of the human pancreas and the risks of immunosuppressive therapy. The implantation of normal islets has met with limited success. The alternative approach, the creation of an artificial pancreas, is now a major area of active investigation. An automated mechanical glucose-responsive sensor-guided insulin infusion system has been a long-term goal. Although significant challenges remain, with improvements in pump therapy and sensor technologies, considerable progress has been made over the past 5 decades. Feasibility studies using delivery of intraperitoneal insulin with implanted pumps and guided by subcutaneous glucose sensors have been successfully conducted in a small number of patients (1). Since insulin is secreted into the portal circulation, this approach has the advantage of more physiological insulin delivery and reduced peripheral hyperinsulinemia. Few studies have administered insulin via intraportal or intraperitoneal routes because they require invasive procedures, and there are concerns about complications such as infections. Subcutaneous insulin pump therapy with real-time continuous glucose monitoring (CGM), an “open-loop” system, is now used in selected individuals for the management of type 1 diabetes. In appropriate people, improved glycemic control and reduction (but not elimination) of hypoglycemia can be realized with the use of these …

Octreotide

Octreotide

Diabetic Patients with Psychiatric Illness

Diabetic patients with co-morbid mental illness are commonly encountered in clinical practice. Not only are diabetes and mental illness both common in the general population, but rates of diabetes are significantly higher in individuals with psychiatric disorders. This paper reviews literature related to the interplay between these pathologies and the consequent clinical challenge faced by physicians. A systematic review was conducted, examining specific aspects of psychiatric illness which may affect diabetic outcomes. Decreased adherence is a feature of many psychiatric conditions, and can have a major effect on diabetic management and development of long term complications. Glycemic regulation may also be complicated by physiologic changes affecting carbohydrate metabolism. Patterns of counter-regulatory hormone secretion are altered in many psychiatric conditions, which may necessitate an altered diabetic treatment regimen. Further difficulties arise as many psychiatric medications have adverse metabolic effects. Diabetic patients with mental illness present a unique clinical challenge as a result of issues related to behaviour, physiology and medications. Clinicians should be able to recognize "problem patients" who may in fact have undiagnosed, treatable, psychiatric pathology. In patients carrying existing diagnoses, complicating factors to diabetic control should be recognized, and steps taken to minimize adverse effects.

Review: Does hypoglycaemia cause cardiovascular events?

Strict glycaemic control is strongly advocated in people with type 2 diabetes to prevent vascular disease. However, the outcomes of two large clinical trials have indicated the potential dangers of pursuing this policy in those at high risk of cardiovascular disease, with an excess of fatal vascular events being associated with a higher frequency of severe hypoglycaemia. Hypoglycaemia secondary to insulin and sulphonylurea therapy is often associated with serious morbidity; anecdotal evidence has long implicated hypoglycaemia as a potential cause of myocardial ischaemia or a cardiac arrhythmia. Hypoglycaemia provokes sympatho-adrenal activation and counterregulatory hormone secretion, which exert pronounced cardiovascular effects. Although well tolerated in healthy people, the superimposition of these profound physiological effects on a diseased coronary vasculature and a dysfunctional cardiac conductive system may induce serious or even fatal cardiovascular events. These risks should influence therapeutic targets and the approach to diabetes management in people with diabetes with established vascular disease in whom exposure to severe hypoglycaemia could be dangerous.

Glucose Control in Critically Ill Patients Using Sliding Mode Control with Robust Differentiators

This paper presents a sliding mode controller for blood glucose control in critically ill patients. Most of the critically ill patients require an insulin infusion to regulate the elevated glucose levels mainly produced by counter-regulatory hormone secretion and insulin resistance. Sliding mode control can successfully handle problems with parameter uncertainties and nonlinearities. Robust differentiators have been incorporated in order to approximate the derivatives that appear in the resulting control law, and to avoid the abrupt changes in the control signal that are produced by the presence of noise and set point changes. The controller has been tested in silico with a literature model. Validation scenarios include parameter uncertainties, sensor noise and set point changes.

Pancreatic α-cell dysfunction in diabetes

A major, yet poorly understood, feature of type 2 diabetes is the excessive hepatic glucose production and the corresponding insulin resistance leading to fasting hyperglycaemia. The tremendous amount of work done to provide the physiological and molecular mechanisms explaining this impairment has led to the emergence of several consensual hypotheses. Among these, is the increased daily and unregulated plasma glucagon concentration in type 2 diabetic patients. Therefore, studies aiming to understand the physiological regulation of glucagon secretion and the corresponding impairment during diabetes are directly relevant to the treatment of type 2 diabetes. Glucagon secretion by α-cells is an immediate response to glucopenia. Abnormal secretion of glucagon and other counterregulatory hormones is a hallmark of type 1 and type 2 diabetes and a major limitation to the use of strong hypoglycaemia agents. A few molecular mechanisms of glucose detection triggering counterregulation and in particular inducing glucagon secretion or suppressing it during hyperglycaemic episodes, have been identified. Such mechanisms are related to those of the insulin secreted β-cell. The glucose transporter GLUT2 and the K-ATP dependent channel, as well as regulatory mechanisms, involved the central nervous system and the gut-brain hormone GLP-1. Over the last years, glucoincretins have provided promising results for the normalization of plasma glucagon concentration of type 2 diabetic patients, which could partly explain the therapeutic benefits of incretin-related therapy. The underlined mechanisms of GLP-1 regulated glucagon secretion are most likely related to the action of the hormone on the activation of the portal and brain glucose sensors. Certainly, strategies aiming to restore glucose-regulated glucagon secretion are important milestones for the treatment of diabetic patient and the prevention of iatrogenic hypoglycaemia.

Hypoglycemia activates arousal-related neurons and increases wake time in adult rats

Hypoglycemia resulting from excess of exogenous or endogenous insulin elicits central nervous system activation that contributes to counterregulatory hormone secretion. In adult humans without diabetes, hypoglycemia occurring during sleep usually produces cortical activation with awakening. However, in adult humans with type 1 diabetes, hypoglycemic arousal appears blunted or absent. We hypothesized that insulin injection sufficient to produce hypoglycemia would induce awakening in adult male rats. Polysomnographic studies were carried out to characterize the effect of insulin injection on measures of sleep and waking during a circadian time of increased sleep. Compared to a baseline day, insulin treatment more than doubled the time spent awake, from 18.4 ± 2.6% after saline injection to 48.0 ± 5.5% after insulin. Insulin injection also reduced rapid eye movement sleep (REMS) from 27.3 ± 1.8% to 5.6 ± 1.3%. The percent of time in non-REM sleep (NREMS) sleep was not different between saline and insulin days, however, NREMS after insulin was fragmented, with increased number and decreased duration of episodes. These electrophysiological data indicate that insulin-induced hypoglycemia is an arousing stimulus in rats, as in nondiabetic adult humans. We also studied the effect of insulin on activation of selected arousal-related neurons using immunohistochemical detection of Fos. Fos-immunoreactivity increased in orexin (OX) neurons after insulin, from 8.7 ± 4.9% after saline injection to 37 ± 9% after insulin. Basal forebrain cholinergic nuclei also showed increased Fos-immunoreactivity after insulin. These correlated behavioral and histological data provide targets for future studies of the neural pathways underlying hypoglycemic arousal.

Role of Hepatic Glycogen Breakdown in Defective Counterregulation of Hypoglycemia in Intensively Treated Type 1 Diabetes

Impairment of hypoglycemic counterregulation in intensively treated type 1 diabetes has been attributed to deficits in counterregulatory hormone secretion. However, because the liver plays a critical part in recovery of plasma glucose, abnormalities in hepatic glycogen metabolism per se could also play an important role. We quantified the contribution of net hepatic glycogenolysis during insulin-induced hypoglycemia in 10 nondiabetic subjects and 7 type 1 diabetic subjects (HbA1c 6.5 +/- 0.2%) using 13C nuclear magnetic resonance spectroscopy, during 2 h of either hyperinsulinemic euglycemia (plasma glucose 92 +/- 4 mg/dl) or hypoglycemia (plasma glucose 58 +/- 3 mg/dl). In nondiabetic subjects, hypoglycemia was associated with a brisk counterregulatory hormone response (plasma epinephrine 246 +/- 38 vs. 2,785 +/- 601 pmol/l during hypoglycemia, plasma norepinephrine 1.9 +/- 0.2 vs. 2.5 +/- 0.3 nmol/l, and glucagon 38 +/- 7 vs. 92 +/- 17 pg/ml, respectively, P < 0.001 in all), and a relative increase in endogenous glucose production (EGP 0.83 +/- 0.14 mg x kg(-1) x min(-1) during euglycemia yet approximately 50% higher with hypoglycemia [1.30 +/- 0.20 mg x kg(-1) x min(-1)], P < 0.001). Net hepatic glycogen content declined progressively during hypoglycemia to 22 +/- 3% below baseline (P < 0.024). By the final 30 min of hypoglycemia, hepatic glycogen fell from 301 +/- 14 to 234 +/- 10 mmol/l (P < 0.001) and accounted for approximately 100% of EGP. In marked contrast, after an overnight fast, hepatic glycogen concentration in type 1 diabetic subjects (215 +/- 23 mmol/l) was significantly lower than in nondiabetic subjects (316 +/- 19 mmol/l, P < 0.001). Furthermore, the counterregulatory response to hypoglycemia was significantly reduced with small increments in plasma epinephrine and norepinephrine (126 +/- 22 vs. 448 +/- 16 pmol/l in hypoglycemia and 0.9 +/- 0.3 vs. 1.6 +/- 0.3 nmol/l, respectively, P < 0.05 for both) and no increase in plasma glucagon. EGP decreased during hypoglycemia with no recovery (1.3 +/- 0.5 vs. 1.2 +/- 0.3 mg x kg(-1) x min(-1) compared with euglycemia, P = NS), and hepatic glycogen concentration did not change significantly with hypoglycemia. We conclude that glycogenolysis accounts for the majority of EGP during the first 90 min of hypoglycemia in nondiabetic subjects. In intensively treated type 1 diabetes, despite some activation of counterregulation, hypoglycemia failed to stimulate hepatic glycogen breakdown or activation of EGP, factors that may contribute to the defective counterregulation seen in such patients.

Hypoglycemia in Type 2 Diabetes

The importance of strict glycemic control to limit the risk of diabetic vascular complications is indisputable, but many barriers obstruct its attainment. Hypoglycemia is recognized to be a major limitation in achieving good control in type 1 diabetes (1) but has been considered to be a minor problem of the treatment modalities used for type 2 diabetes (2). This may be a misperception based on inadequate information. The burden of covert hypoglycemia associated with oral antidiabetic agents may be underestimated, and with the increasing use of insulin to treat type 2 diabetes, the actual prevalence of hypoglycemia is likely to escalate. The frequency and pathophysiology of hypoglycemia in type 2 diabetes and the relationship to different therapies was reviewed by conducting a literature search using the bibliographic database PubMed to identify publications in English from 1984 until 2005 related to hypoglycemia associated with treatment of type 2 diabetes, and the bibliographies of relevant articles were scrutinized for additional citations. Search terms included “type 2 diabetes,” “NIDDM,” “non-insulin-dependent diabetes,” “hypoglycemia,” and “hypoglycaemia.” ### Normal physiological responses to hypoglycemia The human brain primarily uses glucose as its source of energy. Under normal conditions, the brain is unable to synthesize or store glucose and is exquisitely vulnerable to glucose deprivation. To protect the integrity of the brain, several physiological mechanisms have evolved to respond to and limit the effects of hypoglycemia (3–6). In humans, the initial response to a decline in blood glucose is suppression of endogenous insulin secretion followed by release of counterregulatory hormones, of which glucagon and epinephrine (adrenaline) are the most potent. When blood glucose falls in a nondiabetic adult, the secretion of counterregulatory hormones and the onset of cognitive, physiological, and symptomatic changes occur at reproducible blood glucose thresholds (4,7) within a defined hierarchy (5) (Fig. 1). Subjective recognition of …

Hypoglycemia-induced noradrenergic activation in the VMH is a result of decreased ambient glucose

During insulin-induced hypoglycemia, there is an increase in extracellular norepinephrine (NE) in the ventromedial hypothalamus (VMH). This brain area is known to play an important role in integrated hormonal and behavioral responses to systemic hypoglycemia. Selective glucoprivation restricted to the VMH is both necessary and sufficient to initiate secretion of counterregulatory hormones. The present study was designed to investigate whether increased release of NE in the VMH depends on detection of glucoprivation localized in this area. In awake, chronically catheterized male Sprague-Dawley rats, extracellular NE in the VMH was monitored using 1-mm microdialysis probes perfused with Krebs Ringer buffer (KRB) or KRB + 100 mM d-glucose (d-Glc). During insulin-induced hypoglycemia (glycemic nadir approximately 2.4 mM) extracellular NE was increased to >160% of baseline (P < 0.01) only in the KRB + insulin group. There was no increase in NE from baseline when glucose was added to the perfusate to maintain euglycemia at the periprobe environment. The sympathoadrenal response to hypoglycemia, present in the KRB + insulin group, was attenuated in the d-Glc + insulin group. The present results confirm that noradrenergic activation in the VMH during systemic hypoglycemia depends on detection of glucoprivation locally in this area. These data provide additional support for the importance of increased noradrenergic activity in the VMH in the counterregulatory hormonal responses to hypoglycemia.

New Twist on Neuronal Insulin Receptor Signaling in Health, Disease, and Therapeutics

Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer’s disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin’s pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.

Adiponectin and glucose production in patients infected with Plasmodium falciparum

Infections are often complicated by an increase in glucose production due to stimulation of the secretion of glucose counter-regulatory hormones and cytokines. Adiponectin, a fat-derived hormone with insulin-sensitizing properties, could play a regulatory role in the degree of stimulation of glucose production by the infectious agent. Therefore, we investigated the possible correlation between glucose production and plasma adiponectin levels in 25 subjects: 7 patients with cerebral malaria, 6 with uncomplicated malaria, and 12 matched controls. Glucose production was significantly higher in patients with malaria compared to healthy controls ( P < .001). Adiponectin levels were not different between the patients with malaria and the control group. However, patients with cerebral malaria had significantly higher values for adiponectin than the patients with uncomplicated malaria ( P < .005). Glucose production and gluconeogenesis were positively correlated to plasma adiponectin in the patients ( r = 0.835, P < .001 and r = 0.846, P < .001, respectively), whereas these correlations were absent in the controls ( r = −0.329, NS and r = −0.028, NS, respectively). In conclusion, adiponectin levels were not different between patients with malaria and their matched controls. However, patients infected with Plasmodium falciparum who have higher glucose production also have higher adiponectin levels. In healthy subjects such a correlation was not found. As adiponectin is known to inhibit glucose production, stimulation of adiponectin secretion during infection could be intended to restrain the glucose production stimulating properties of hormones and cytokines secreted during infection.