Unexpected role for IGF-1 in starvation: Maintenance of blood glucose.

Wild-type (WT) mice maintain viable levels of blood glucose even when adipose stores are depleted by 6 d of 60% calorie restriction followed by a 23-h fast (hereafter designated as "starved" mice). Survival depends on ghrelin, an octanoylated peptide hormone. Mice that lack ghrelin suffer lethal hypoglycemia when subjected to the same starvation regimen. Ghrelin is known to stimulate secretion of growth hormone (GH), which in turn stimulates secretion of IGF-1 (insulin-like growth factor-1). In the current study, we found that starved ghrelin-deficient mice had a 90% reduction in plasma IGF-1 when compared with starved WT mice. Injection of IGF-1 in starved ghrelin-deficient mice caused a twofold increase in glucose production and raised blood glucose to levels seen in starved WT mice. Increased glucose production was accompanied by increases in plasma glycerol, fatty acids and ketone bodies, and hepatic triglycerides. All of these increases were abolished when the mice were treated with atglistatin, an inhibitor of adipose tissue triglyceride lipase. We conclude that IGF-1 stimulates adipose tissue lipolysis in starved mice and that this lipolysis supplies energy and substrates that restore hepatic gluconeogenesis. This action of IGF-1 in starved mice is in contrast to its known action in inhibiting adipose tissue lipase in fed mice. Surprisingly, the ghrelin-dependent maintenance of plasma IGF-1 in starved mice was not mediated by GH. Direct injection of GH into starved ghrelin-deficient mice failed to increase plasma IGF-1. These data call attention to an unsuspected role of IGF-1 in the adaptation to starvation.

Differential protein expression of mitogen-activated protein kinases in erythrocytes and liver of lamprey Lampetra fluviatilis on the course of prespawning starvation.

The study was designed to identify the types of mitogen-activated protein kinases (MAPKs) in erythrocytes and liver tissues of river lamprey Lampetra fluviatilis and monitor the changes in protein expression levels of found enzymes on the course of prespawning starvation (from November to the end of May). Immunoreactivity of the native and phosphorylated forms of ERK1/2, JNK and p38 was examined in the cytosolic and membrane cell fractions. Both lamprey erythrocytes and liver were found to highly express ERK1/2 and JNK, whereas only trace amounts of p38 were revealed in hepatic tissues. ERK1/2 was identified in cytosolic and membrane fractions, whereas JNK and p38 were predominantly cytosolic enzymes. Total cellular amounts of ERK1/2 and phospho-ERK1/2 in both erythrocytes and liver tissues appeared to be relatively stable on the course of prespawning starvation. However, before spawning ERK1/2 translocated from cytosol to membranes, with partial decline of its cytoplasmic expression being compensated by increases in membrane-bound pool. Immunoreactivity of cytoplasmic JNK, phospho-JNK and p38 were stable from November to March, but sharply decreased before spawning exhibiting almost negligible levels in May, which suggests the depletion of their cellular fractions. Most probably, ERK1/2 plays more important role in mediating adaptive responses of erythrocytes and liver tissues to conditions of natural starvation and maintenance of cell viability before spawning and death of animals in May.

Metabolome Characteristics of Liver Autophagy Deficiency under Starvation Conditions in Infancy.

The liver function is essential for metabolism, detoxification, and bile synthesis, even in the neonatal period. Autophagy plays significance roles in THE adult liver, whereas the role of liver autophagy in the early neonatal period largely remains unclear. To clarify the importance of liver autophagy in the neonatal starvation period, we generated liver-specific autophagy-deficient (Atg5flox/flox; Albumin-Cre) mice and investigated under starvation conditions comparing with control (Atg5flox/+; Albumin-Cre) mice, focusing on serum metabolites and liver histopathology. As a result, autophagy in the liver was found to unessential for the survival under postnatal starvation. A metabolomics analysis of serum metabolites by gas chromatography-tandem mass spectrometry showed a significant difference between the groups, especially after 12-h starvation, suggesting the synergistical adaption of metabolic pathways, such as the "malate-aspartate shuttle", "aspartate metabolism", "urea cycle", and "glycine and serine metabolism". Liver-specific autophagy-deficiency under postnatal starvation conditions can cause a characteristic metabolic alteration suggesting a change of the mitochondrial function. Neonates seemed to maintain ketone production under starvation conditions, even in the autophagy-deficient liver, through a change in the mitochondrial function, which may be an adaptive mechanism for avoiding fatal starvation.

[Starvation ketoacidosis during prolonged fasting of 26 days]. / Hypercétose dans un contexte de jeûne prolongé de 26 jours.

Ketosis is a metabolic situation involving an increase in blood and urine concentrations of ketones that, when prolonged, leads to acidosis. Moderate ketosis usually appears after a fast of a few hours, but its prolongation exposes to hyperketosis. Observation: A 25-year-old woman presented to the emergency department for cohercitive vomiting. She was fasting for a long time in a spiritual setting and had a restricted diet limited to water and vitamin supplements. Clinical and biological assessment was in favour of fasting ketoacidosis. Evolution was favorable with intravenous hydration, poly-ionic and micronutrient supplementation and a gradual resumption of oral feeding. Conclusion: We report the case of a patient with fasting ketoacidosis. Besides consequences of this ketoacidosis, the challenge was also in resuming oral feeding in order to avoid a potentially fatal inappropriate renutrition syndrome.

Growth hormone acts on liver to stimulate autophagy, support glucose production, and preserve blood glucose in chronically starved mice.

When mice are subjected to 60% calorie restriction for several days, they lose nearly all of their body fat. Although the animals lack energy stores, their livers produce enough glucose to maintain blood glucose at viable levels even after a 23-hour fast. This adaptation is mediated by a marked increase in plasma growth hormone (GH), which is elicited by an increase in plasma ghrelin, a GH secretagogue. In the absence of ghrelin, calorie-restricted mice develop hypoglycemia, owing to diminished glucose production. To determine the site of GH action, in the current study we used CRISPR/Cas9 and Cre recombinase technology to produce mice that lack GH receptors selectively in liver (L-Ghr-/- mice) or in adipose tissue (Fat-Ghr-/- mice). When subjected to calorie restriction and then fasted for 23 hours, the L-Ghr-/- mice, but not the Fat-Ghr-/- mice, developed hypoglycemia. The fall in blood glucose in L-Ghr-/- mice was correlated with a profound drop in hepatic triglycerides. Hypoglycemia was prevented by injection of lactate or octanoate, two sources of energy to support gluconeogenesis. Electron microscopy revealed extensive autophagy in livers of calorie-restricted control mice but not in L-Ghr-/- mice. We conclude that GH acts through its receptor in the liver to activate autophagy, preserve triglycerides, enhance gluconeogenesis, and prevent hypoglycemia in calorie-restricted mice, a model of famine.

Relationship between polyunsaturated fatty acid and eating disorders: Systematic review and meta-analysis.

OBJECTIVES: Eating disorders result in poor nutrition, poor physical conditions and even suicidality and mortality. Although polyunsaturated fatty acids (PUFAs) have attracted attention in the emerging field of nutritional psychiatry, their role in eating disorders remains unknown. This meta-analysis investigates the differences of PUFA levels between patients with eating disorders and healthy controls, and the potentially beneficial effects of PUFAs in such patients. METHODS: We conducted a systematic literature search and meta-analysis under the random effects model. RESULT: Eleven studies were included in the current meta-analysis. Compared with controls, 379 patients with eating disorders had significantly higher plasma levels of alpha-linolenic acid, eicosapentaenoic acid, stearidonic acid, osbond acid, palmitoleic acid, oleic acid, and total omega-3 fatty acids; and lower levels of total omega-6 fatty acids and omega-6/omega-3 ratio. Eating disorders were associated with significantly higher red blood cell membrane levels of palmitoleic acid and oleic acid and lower levels of adrenic acid, arachidonic acid, and total omega-6 fatty acids. In addition, PUFA supplements were associated with a benefit to body weight outcomes but not disease severity and mood symptoms in interventional trials. DISCUSSION: This meta-analysis indicates abnormal levels of PUFAs in peripheral blood tissues in patients with eating disorders. The relationship between PUFAs and eating disorders should be interpreted cautiously considering the specific lipid metabolism under starvation state. To investigate the role of PUFAs on psychopathological and therapeutic effects in eating disorders, further larger clinical studies are warranted.

Human PBMCs fight or flight response to starvation stress: Increased T-reg, FOXP3, and TGF-ß1 with decreased miR-21 and Constant miR-181c levels.

Regulatory T-lymphocytes play a prominent role in autoimmunity, allergy, and cancer. In some conditions such as inflammation and tumor, immune cells are encountered with metabolic stress. Emerging evidence indicates the contribution of microRNAs in both metabolism and immune regulation. Herewith, we have examined the in vitro effects of serum starvation for 16, 48, 72 and 96 h on the expression of T-reg differentiation markers (CD4, CD25, CD127, and FOXP3) as well as on the Transforming Growth Factor-ß1 (TGF-ß1) and some microRNAs (miR-21,-29a,-31,146a,-155,-181a and -181c) levels in human Peripheral Blood Mononuclear Cells (PBMCs). The percentage of CD4+CD25+CD127low/-FOXP3+ T-regs, as well as FOXP3 expression, was increased in starved lymphocytes (p < 0.01). 96 h-starved PBMCs had the lowest T-eff/T-reg ratio (p < 0.05). All the studied miRNAs except miR-181c were significantly down-regulated in those cells (p < 0.05), in particular, miR-29a and miR-155 were sharply declined in 48h-starved PBMCs (p < 0.01). There was a negative correlation between time of starvation and microRNAs expression, except for miR-181c (r-value = -0. 61 to -0.9 and p-value = 0.037 to 0). The percentage of T-reg was inversely correlated with all miRNAs levels except for miR-31 and miR-181c (r-value = -0.68 to -0.78 and p-value = 0.015 to 0.003). FOXP3 expression exhibited a same degree of negative correlation with miR-31 and miR-155 expression levels (r = -0.57 and p = 0.05, for both). Increasing starvation duration led to a rise inTGF-ß1 protein levels (p<0.01), especially its active form (P<0.001). This study introduced the serum starvation as a tool for immunoregulation which acts probably through increasing TGF-ß1 production and inducing some alterations in microRNAs expression.

The circulating metabolome of human starvation.

The human adaptive starvation response allows for survival during long-term caloric deprivation. Whether the physiology of starvation is adaptive or maladaptive is context dependent: activation of pathways by caloric restriction may promote longevity, yet in the context of caloric excess, the same pathways may contribute to obesity. Here, we performed plasma metabolite profiling of longitudinally collected samples during a 10-day, 0-calorie fast in humans. We identify classical milestones in adaptive starvation, including the early consumption of gluconeogenic amino acids and the subsequent surge in plasma nonesterified fatty acids that marks the shift from carbohydrate to lipid metabolism, and demonstrate findings, including (a) the preferential release of unsaturated fatty acids and an associated shift in plasma lipid species with high degrees of unsaturation and (b) evidence that acute, starvation-mediated hypoleptinemia may be a driver of the transition from glucose to lipid metabolism in humans.

Metabolic effects of fasting on human and mouse blood in vivo.

Starvation is a strong physiological stimulus of macroautophagy/autophagy. In this study, we addressed the question as to whether it would be possible to measure autophagy in blood cells after nutrient deprivation. Fasting of mice for 48 h (which causes ∼20% weight loss) or starvation of human volunteers for up to 4 d (which causes <2% weight loss) provokes major changes in the plasma metabolome, yet induces only relatively minor alterations in the intracellular metabolome of circulating leukocytes. White blood cells from mice and human volunteers responded to fasting with a marked reduction in protein lysine acetylation, affecting both nuclear and cytoplasmic compartments. In circulating leukocytes from mice that underwent 48-h fasting, an increase in LC3B lipidation (as assessed by immunoblotting and immunofluorescence) only became detectable if the protease inhibitor leupeptin was injected 2 h before drawing blood. Consistently, measurement of an enhanced autophagic flux was only possible if white blood cells from starved human volunteers were cultured in the presence or absence of leupeptin. Whereas all murine leukocyte subpopulations significantly increased the number of LC3B+ puncta per cell in response to nutrient deprivation, only neutrophils from starved volunteers showed signs of activated autophagy (as determined by a combination of multi-color immunofluorescence, cytofluorometry and image analysis). Altogether, these results suggest that white blood cells are suitable for monitoring autophagic flux. In addition, we propose that the evaluation of protein acetylation in circulating leukocytes can be adopted as a biochemical marker of organismal energetic status.

Euglycemic Diabetic Ketoacidosis: A Review.

INTRODUCTION: Diabetic ketoacidosis (DKA) is one of the most serious complications of diabetes. It is characterised by the triad of hyperglycemia (blood sugar >250 mg/dl), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L) and ketosis. Rarely these patients can present with blood glucose (BG) levels of less than 200 mg/dl, which is defined as euglycemic DKA. The possible etiology of euglycemic DKA includes the recent use of insulin, decreased caloric intake, heavy alcohol consumption, chronic liver disease and glycogen storage disorders. DKA in pregnancy has also been reported to present with euglycemia. The recent use of sodium glucose cotransporter 2 (SGLT2) inhibitors has shed light on another possible mechanism of euglycemic DKA. Clinicians may also be misled by the presence of pseudonormoglycemia. CONCLUSION: Euglycemic DKA thus poses a challenge to physicians, as patients presenting with normal BG levels in ketoacidosis may be overlooked, leading to a delay in appropriate management strategies. In this article, we review all the possible etiologies and the associated pathophysiology of patients presenting with euglycemic DKA. We also discuss the approach to diagnosis and management of such patients. Despite euglycemia, ketoacidosis in diabetic patients remains a medical emergency and must be treated in a quick and appropriate manner.

Starvation Ketoacidosis as a Cause of Unexplained Metabolic Acidosis in the Perioperative Period.

BACKGROUND Besides providing anesthesia for surgery, the anesthesiologist's role is to optimize the patient for surgery and for post-surgical recovery. This involves timely identification and treatment of medical comorbidities and abnormal laboratory values that could complicate the patient's perioperative course. There are several potential causes of anion and non-anion gap metabolic acidosis in surgical patients, most of which could profoundly affect a patient's surgical outcome. Thus, the presence of an acute acid-base disturbance requires a thorough workup, the results of which will influence the patient's anesthetic management. CASE REPORT An otherwise-healthy 24-year-old female presented for elective spine surgery and was found to have metabolic acidosis, hypotension, and polyuria intraoperatively. Common causes of acute metabolic acidosis were investigated and systematically ruled out, including lactic acidosis, diabetic ketoacidosis, drug-induced ketoacidosis, ingestion of toxic alcohols (e.g., methanol, ethylene glycol), uremia, and acute renal failure. Laboratory workup was remarkable only for elevated serum and urinary ketone levels, believed to be secondary to starvation ketoacidosis. Due to the patient's unexplained acid-base disturbance, she was kept intubated postoperatively to allow for further workup and management. CONCLUSIONS Starvation ketoacidosis is not widely recognized as a perioperative entity, and it is not well described in the medical literature. Lack of anesthesiologist awareness about this disorder may complicate the differential diagnosis for acute intraoperative metabolic acidosis and lead to a prolonged postoperative stay and an increase in hospital costs. The short- and long-term implications of perioperative ketoacidosis are not well defined and require further investigation.

Altered metabolic homeostasis is associated with appetite regulation during and following 48-h of severe energy deprivation in adults.

BACKGROUND: Military personnel frequently endure intermittent periods of severe energy deficit which can compromise health and performance. Physiologic factors contributing to underconsumption, and the subsequent drive to overeat, are not fully characterized. This study aimed to identify associations between appetite, metabolic homeostasis and endocrine responses during and following severe, short-term energy deprivation. METHODS: Twenty-three young adults (17M/6F, 21±3years, BMI 25±3kg/m(2)) participated in a randomized, controlled, crossover trial. During separate 48-h periods, participants increased habitual energy expenditure by 1647±345kcal/d (mean±SD) through prescribed exercise at 40-65% VO2peak, and consumed provided isovolumetric diets designed to maintain energy balance at the elevated energy expenditure (EB; 36±93kcal/d energy deficit) or to produce a severe energy deficit (ED; 3681±716kcal/d energy deficit). Appetite, markers of metabolic homeostasis and endocrine mediators of appetite and substrate availability were periodically measured. Ad libitum energy intake was measured over 36h following both experimental periods. RESULTS: Appetite increased during ED and was greater than during EB despite maintenance of diet volume (P=0.004). Ad libitum energy intake was 907kcal/36h [95% CI: 321, 1493kcal/36h, P=0.004] higher following ED compared to following EB. Serum beta-hydroxybutyrate, free fatty acids, branched-chain amino acids, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol concentrations were higher (P<0.001 for all), whereas whole-body protein balance was more negative (P<0.001), and serum glucose, insulin, and leptin concentrations were lower (P<0.001 for all) during ED relative to during EB. Cortisol concentrations, but not any other hormone or metabolic substrate, were inversely associated with satiety during EB (R(2)=0.23, P=0.04). In contrast, serum glucose and DHEA-S concentrations were inversely associated with satiety during ED (R(2)=0.68, P<0.001). No associations between physiologic variables measured during EB and ad libitum energy intake following EB were observed. However, serum leptin and net protein balance measured during ED were inversely associated with ad libitum energy intake following ED (R(2)=0.48, P=0.01). CONCLUSION: These findings suggest that changes in metabolic homeostasis during energy deprivation modulate appetite independent of reductions in diet volume. Following energy deprivation, physiologic signals of adipose and lean tissue loss may drive restoration of energy balance. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov #NCT01603550.

FGF21 and the late adaptive response to starvation in humans.

In mice, FGF21 is rapidly induced by fasting, mediates critical aspects of the adaptive starvation response, and displays a number of positive metabolic properties when administered pharmacologically. In humans, however, fasting does not consistently increase FGF21, suggesting a possible evolutionary divergence in FGF21 function. Moreover, many key aspects of FGF21 function in mice have been identified in the context of transgenic overexpression or administration of supraphysiologic doses, rather than in a physiologic setting. Here, we explored the dynamics and function of FGF21 in human volunteers during a 10-day fast. Unlike mice, which show an increase in circulating FGF21 after only 6 hours, human subjects did not have a notable surge in FGF21 until 7 to 10 days of fasting. Moreover, we determined that FGF21 induction was associated with decreased thermogenesis and adiponectin, an observation that directly contrasts with previous reports based on supraphysiologic dosing. Additionally, FGF21 levels increased after ketone induction, demonstrating that endogenous FGF21 does not drive starvation-mediated ketogenesis in humans. Instead, a longitudinal analysis of biologically relevant variables identified serum transaminases--markers of tissue breakdown--as predictors of FGF21. These data establish FGF21 as a fasting-induced hormone in humans and indicate that FGF21 contributes to the late stages of adaptive starvation, when it may regulate the utilization of fuel derived from tissue breakdown.

Behavioural and physiological responses of wood mice (Apodemus sylvaticus) to experimental manipulations of predation and starvation risk.

Body weight and the levels of stored body fat have fitness consequences. Greater levels of fat may provide protection against catastrophic failures in the food supply, but they may also increase the risk of predation. Animals may therefore regulate their fatness according to their perceived risks of predation and starvation: the starvation-predation trade-off model. We tested the predictions of this model in wood mice (Apodemus sylvaticus) by experimentally manipulating predation risk and starvation risk. We predicted that under increased predation risk individuals would lose weight and under increased starvation risk they would gain it. We simulated increased predation risk by playing the calls made by predatory birds (owls: Tyto alba and Bubo bubo) to the mice. Control groups included exposure to calls of a non-predatory bird (blackbird: Turdus merula) or silence. Mice exposed to owl calls at night lost weight relative to the silence group, mediated via reduced food intake, but exposure to owl calls in the day had no significant effect. Exposure to blackbird calls at night also resulted in weight loss, but blackbird calls in the day had no effect. Mice seemed to have a generalised response to bird calls at night irrespective of their actual source. This could be because in the wild any bird calling at night will be a predation risk, and any bird calling in the day would not be, because at that time the mice would normally be resting, and hence not exposed to avian predators. Consequently, mice have not evolved to distinguish different types of call but only to respond to the time of day that they occur. Mice exposed to stochastic 24h starvation events altered their behaviour (reduced activity) during the refeeding days that followed the deprivation periods to regain the lost mass. However, they only marginally elevated their food intake and consequently had reduced body weight/fat storage compared to that of the control unstarved group. This response may have been constrained by physiological factors (alimentary tract absorption capacity) or behavioural factors (perceived risk of predation). Overall the responses of the mice appeared to provide limited support for the starvation-predation trade-off model, and suggest that wood mice are much more sensitive to predation risk than they are to starvation risk.

Prenatal undernutrition and leukocyte telomere length in late adulthood: the Dutch famine birth cohort study.

BACKGROUND: Energy restriction in prenatal life has detrimental effects on later life health and longevity. Studies in rats have shown that the shortening of telomeres in key tissues plays an important role in this association. OBJECTIVE: The aim of the current study was to investigate leukocyte telomere length in relation to prenatal famine exposure. DESIGN: The Dutch famine birth cohort consists of 2414 term singleton men and women who were born between 1943 and 1947 in Amsterdam around the time of the famine. At a mean age of 68 y, telomere length and the percentage of short telomeres was assessed in a subsample of 131 cohort members, of whom 45 were born before the famine (control), 41 were exposed to famine during early gestation, and 45 were conceived after the famine (control). Median telomere length was determined in peripheral blood leukocytes by a high-throughput quantitative fluorescent in situ hybridization-based technology. RESULTS: Leukocyte telomere length and the percentage of short telomeres did not differ between those exposed to famine during early gestation and those unexposed during gestation. A lower socioeconomic status at birth, frequent consumption of alcohol (specifically consumption of spirits), a history of cancer, and a lower self-reported health status were significantly associated with shorter leukocyte telomere length (all P ≤ 0.03). Currently having a job was significantly associated with a smaller percentage of short telomeres (P = 0.04). CONCLUSION: The results of the current study suggest that prenatal exposure to famine is not associated with the shortening of telomeres in peripheral blood leukocytes at age 68 y.

Acetone as biomarker for ketosis buildup capability--a study in healthy individuals under combined high fat and starvation diets.

BACKGROUND: Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy. METHODS: A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual's energy expenditure. On Day 7, ketone buildup from FK was measured. RESULTS: A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p < 0.0058. Using a Fisher LDS pair-wise comparison, higher significant levels of acetone buildup were found for diets with 79% fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content. In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R(2) = 0.92), and lower body mass index (R(2) = 0.71) was observed during FK.

Malnutrition-induced Wernicke's encephalopathy following a water-only fasting diet.

BACKGROUND: Wernicke's encephalopathy is a critical condition of neurological dysfunction resulting from a deficiency in thiamine. Chronic alcoholism is recognized as the most common cause of Wernicke's encephalopathy, but other causes, including fasting/starvation and malnutrition, have been documented within the scientific literature. These causes may not be readily recognized by healthcare professionals and may lead to Wernicke's encephalopathy being overlooked as a diagnosis when a nonalcoholic patient presents with classic signs and symptoms of the disorder. MATERIALS AND METHODS: A narrative review of thiamine and its relationship to the development, diagnosis, and treatment of Wernicke's encephalopathy is presented based on a review of evidence-based guidelines and published research. To heighten awareness of the development of Wernicke's encephalopathy in fasted/starved and malnourished patients and to contribute to the scientific body of knowledge for the identification and management of Wernicke's encephalopathy in these patients, the clinical course and treatment of an adult woman who developed Wernicke's encephalopathy following a 40-day water-only fasting diet is outlined. RESULTS: Clinical suspicion was required to identify the patient's condition and initiate immediate intervention through parenteral thiamine administration. Oral thiamine supplementation of 100 to 800 mg per day for 6 months was required to aid recovery. OUTCOMES: The patient's clinical course and response to treatment illustrate the necessity for clinical awareness and suspicion of Wernicke's encephalopathy among healthcare professionals, timely and adequate parenteral thiamine administration, and oral thiamine supplementation at therapeutic doses to correct the nutrient deficiency, halt the progression of Wernicke's encephalopathy, and promote recovery.

Famines in the last 100 years: implications for diabetes.

Overnutrition is a major cause of diabetes. The contrary situation of undernutrition has also been suggested to increase the risk of the disease. Especially undernutrition during prenatal life has been hypothesized to program the structure and physiology of the fetus in such a way that it is more prone to develop diabetes in later life. Famines over the last 100 years have provided historical opportunities to study later-life health consequences of poor nutritional circumstances in early life. The majority of studies based on famine exposure during prenatal life clearly show that diabetes risk is increased. Postnatal famine exposure in childhood, adolescence, or young adulthood also seems to raise risk for diabetes, although prenatal famine effects seem to be more substantial. These study results not only have implications for the consequences of famines still happening but also for pregnancies complicated by factors mimicking poor nutritional situations.

Refractory hypoglycemia and subsequent cardiogenic shock in starvation and refeeding: report of three cases.

OBJECTIVE: Although starvation is associated with high in-hospital mortality, its related cardiac complications are not sufficiently understood. The aim of this study was to determine the clinical course and pathogenesis of cardiac complications in malnourished patients. METHODS: We reviewed three cases of hypoglycemia and hypotriglyceridemia with cardiac complications in starvation. RESULTS: This report concerns three patients, respectively suffering from anorexia nervosa, esophageal carcinoma, and Parkinson's disease. Their ages ranged from 18 to 70 y, body mass index was 11.5 ± 1.5 kg/m2 (mean ± SD), and the main symptom was coma. The average blood glucose level was 15.7 ± 7.8 mg/dL without any history of insulin use or diabetes mellitus. In all cases, hypoglycemia was refractory and repetitive so that continuous glucose administration was required to maintain euglycemia. Serum triglyceride and non-esterified fatty acid levels were also very low (7 ± 4 mg/dL and 10 ± 9.1 µEq/L, respectively). Levels of serum potassium, phosphate, and magnesium were almost normal at admission. The main cardiac complications included Takotsubo cardiomyopathy and cardiac arrest. All patients survived as a result of intensive treatment. CONCLUSIONS: Repetitive severe hypoglycemia without known background causes should be viewed as an important sign. Once this occurs, the administration of a much higher caloric input than usual accompanied by intensive monitoring will be required to maintain appropriate glucose levels. The early identification of such patients seems to be essential to reduce the high risk for cardiac complications during starvation and refeeding.