Olanzapine-induced glucose dysregulation

OBJECTIVE: To report a patient who developed severe exacerbation of type 2 diabetes mellitus after the initiation of olanzapine therapy. CASE SUMMARY: A 54-year-old African-American woman developed severe glucose dysregulation 12 days after the initiation of olanzapine. Prior to starting olanzapine therapy, the patient's diabetes was controlled by diet modification with a glycosylated hemoglobin of 6.5%. During olanzapine therapy, blood glucose concentrations could not be regulated despite use of antidiabetic agents, insulin, and dietary interventions. The patient also gained a total of 13 kg. Two weeks after discontinuation of all antipsychotic medications (olanzapine, quetiapine), the patient's blood glucose concentrations became better regulated and remained better controlled until discharge. DISCUSSION: All atypical antipsychotics are associated with weight gain. Obesity is a well-documented risk factor for developing type 2 diabetes mellitus. Currently there are only six published reports that implicate olanzapine as being associated with glucose dysregulation. The exact cause of glucose dysregulation with olanzapine is unclear, but weight gain does not seem to be the sole etiology. It has been hypothesized that serotonin (5-HT1A) antagonism may decrease the responsiveness of the pancreatic beta-cells. This would then result in inappropriately low insulin secretion and, therefore, hyperglycemia. Based on the Naranjo probability scale, the likelihood that olanzapine caused the glucose dysregulation in our patient was possible. CONCLUSIONS: Although olanzapine has shown greater clinical efficacy and is associated with fewer extrapyramidal side effects than typical antipsychotics, it may produce exacerbation or new emergence of diabetes mellitus. Further examination of the incidence and etiology of glucose dysregulation after the initiation of olanzapine therapy is necessary.     

Initial Combination with Linagliptin and Metformin in Newly Diagnosed Type 2 Diabetes and Severe Hyperglycemia

Making appropriate treatment decisions for patients newly diagnosed with type 2 diabetes mellitus (T2DM) and severe hyperglycemia (glycated hemoglobin [HbA1c] >10% or fasting plasma glucose ≥250 mg/dL) presents a formidable challenge to primary care physicians. Extreme defects in insulin secretion make it unlikely that these patients will achieve glycemic targets with metformin monotherapy. Additionally, uncontrolled hyperglycemia is associated with an increased risk of short-term acute complications, such as hyperosmolar coma, and long-term complications affecting the micro- and macrovasculature. Thus, severely hyperglycemic patients require prompt, intensive treatment to re-establish glycemic control. Current guidelines indicate that either initial insulin therapy or initial combination therapy with metformin plus non-insulin drug(s) are the treatments of choice for these challenging-to-treat patients. This mini-review examines the clinical evidence supporting these two treatment options, with particular reference to the findings of a phase 3 study of treatment with an initial combination of metformin plus the dipeptidyl peptidase-4 inhibitor, linagliptin. Intensive insulin therapy can induce sustained euglycemia and improve beta-cell function in newly diagnosed patients. However, insulin use is associated with an increased risk of adverse events, such as hypoglycemia and weight gain. These potentially serious side effects cause concern among patients and physicians, and are a major barrier to initiating and maintaining adherence to insulin treatment. In the phase 3 study, open-label treatment of severely hyperglycemic patients (HbA1c ≥11.0%) with linagliptin plus metformin resulted in a mean change in HbA1c of ?3.7% ± 1.7%. This combination therapy was generally well tolerated with most adverse events being of mild or moderate intensity; asymptomatic hypoglycemia was reported by just 1 of 66 (1.5%) patients. These findings provide evidence in support of linagliptin plus metformin as a well-tolerated and effective treatment alternative to insulin for new-onset patients with T2DM and severe hyperglycemia.     

Nonketotic hyperosmolar coma in a patient with type 1 diabetes-related diabetic nephropathy: Case report

Nonketotic hyperosmolar coma (NHC) is characterized by severe hyperglycemia; absence of, or only slight ketosis; nonketotic acidosis; severe dehydration; depressed sensorium or frank coma; and various neurologic signs. This condition is uncommon in type 1 diabetes. Because of little or no osmotic diuresis in patients with diabetic nephropathy, increases in plasma osmolality and therefore the likelihood of neurologic symptoms are limited. A 20-year-old male patient with type 1 diabetes with chronic kidney disease on conservative treatment (glomerular filtration rate [GFR], 18 mL/dk) presented with acute nonketotic hyperosmolar syndrome. The patient was admitted presenting with thirst, fatigue, and drowsiness. Blood biochemistry levels were urea 87 mg/dL, creatinine 5.09 mg/dL, glucose 830 mg/dL, glycosylated hemoglobin (HbA_1c) 8%, C peptide < 0.3 ng/mL, sodium 131 mmol/L, chloride 93 mmol/L, potassium 5.2 mmol/L, and calculated serum osmolality 385 mOsm/kg. The presumptive diagnosis on admission was nonketotic hyperosmolar syndrome precipitated by urinary infection. This is the first case report of hyperosmolar coma in a patient with type 1 diabetes with chronic kidney disease.     

Management of the hyperosmolar hyperglycemic syndrome.

Hyperglycemic hyperosmolarity is part of a clinical spectrum of severe hyperglycemic disorders ranging from pure hyperglycemic hyperosmolarity without ketosis to diabetic ketoacidosis, with significant overlap in the middle. From 50 to 75 percent of hospitalizable patients who have uncontrolled diabetes present with significant hyperosmolarity. An altered state of consciousness attributable to uncontrolled diabetes is virtually always the result of severe hyperosmolar hyperglycemia. The linchpin of therapy is prompt, rapid administration of crystalloid solutions that have tonicity appropriate to the level of hyperosmolarity. A decrease in the plasma glucose concentration indicates the adequacy of therapy, especially rehydration; the goal is for the plasma glucose level to decline by at least 75 to 100 mg per dL (4.2 to 5.6 mmol per L) per hour. Patients with hyperosmolar hyperglycemic syndrome are often chronically ill, and they may have major total body deficits of potassium, phosphate and magnesium, as well as B-complex vitamins (especially thiamine). These deficits also require attention and correction during therapy.     

Gatifloxacin-induced hyperglycemia: a case report and summary of the current literature

BACKGROUND: Gatifloxacin is a fluoroquinolone antibiotic that has been associated with severe hypoglycemic and hyperglycemic events. OBJECTIVE: The purpose of this report was to describe a new case of gatifloxacin-associated hyperglycemia in an elderly patient and to provide a summary of case reports. CASE SUMMARY: A male patient, aged 86 years, was hospitalized with small bowel obstruction due to adhesions from a previous appendectomy. At the time of admission, the patient weighed 78.5 kg (ideal body weight, 73 kg), had a body mass index of 24.8 kg/m2, and had a calculated creatinine clearance of 45.6 mL/min. The patient's hospital medications were metoprolol, diltiazem, subcutaneous heparin, ranitidine, vancomycin, piperacillin/tazobactam, and aspirin. He also was treated with gatifloxacin 400 mg QD for suspected pneumonia during the hospital stay. After 4 days of the gatifloxacin regimen, the patient's mean blood glucose concentration increased from 133 mg/dL at the time of admission to 537 mg/dL. Although the patient exhibited signs of glycosuria (ie, urine glucose concentration >1000 mg/dL), he did not complain of symptoms of hyperglycemia, such as polyuria, polyphagia, or polydipsia. The hyperglycemia resolved after administration of gatifloxacin was discontinued and the patient had received regular insulin 15 U SC over 5 hours. DISCUSSION: The exact mechanism by which gatifloxacin induces hyperglycemia is unknown, but it may be related to vacuolation of pancreatic beta-cells, leading to a decrease in insulin secretion. This case, along with the 15 other summarized cases, adds to the evidence for an association between gatifloxacin and hyperglycemia. These patients had other risk factors that may have contributed to the development of hyperglycemia, including age >65 years and renal impairment. CONCLUSION: An elderly patient with no history of diabetes developed severe hyperglycemia after receiving doses of gatifloxacin 400 mg that had not been adjusted for age-related renal impairment. The hyperglycemia resolved after discontinuation of gatifloxacin.     

Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients

OBJECTIVE: The purpose of this study was to assess if hyperglycemia influences energy expenditure or the extent of muscle protein catabolism in severely burned adults. DESIGN: Retrospective study. SETTING: Burn intensive care unit at a university hospital. PATIENTS: Adults with burns on >/=40% of their body surface area. INTERVENTIONS: Simultaneous measurement of indirect calorimetry and leg net balance of phenylalanine (as an index of muscle protein catabolism). Patients were stratified by plasma glucose values at the time of metabolic measurements (i.e., normal, glucose at 200 mg/dL). MEASUREMENTS AND MAIN RESULTS: Normal (n = 9; plasma glucose, 109 +/- 13 mg/dL [mean +/- sd]), mildly hyperglycemic (n = 13l plasma glucose, 156 +/- 17 mg/dL), and severely hyperglycemic subjects (n = 7, glucose 231 +/- 32 mg/dL) were similar in age, body weight, extent of burn area, and daily caloric intake. Severe hyperglycemia was associated with significantly higher arterial concentrations of phenylalanine (normal, 0.079 +/- 0.027 micromol/L; severe hyperglycemia, 0.116 +/- 0.028; p <.05) and a significantly greater net efflux of phenylalanine from the leg (normal, -0.067 +/- 0.072 micromol.min(-1).100 mL(-1) leg volume; severe hyperglycemia, -0.151 +/- 0.080 micromol.min(-1).100 mL(-1) leg volume; p <.05). Resting energy expenditure and respiratory quotient were similar between patient groups. CONCLUSIONS: These findings demonstrate an association between hyperglycemia and an increased rate of muscle protein catabolism in severely burned patients. This suggests a possible link between resistance of muscle to the action of insulin for both glucose clearance and muscle protein catabolism.     

Possible gatifloxacin-induced hyperglycemia

OBJECTIVE: To report a case of possible gatifloxacin-induced hyperglycemia in a nondiabetic middle-aged woman. CASE SUMMARY: A 64-year-old Indian woman with an extensive cardiovascular history was admitted for urosepsis. On admission, her blood glucose was 117 mg/dL. She was empirically started on gatifloxacin 400 mg/day; after 3 days of gatifloxacin therapy, her blood glucose was 607 mg/dL. On day 4, therapy was changed to cefazolin for sensitive Escherichia coli and her blood glucose levels began to return to normal. DISCUSSION: Although gatifloxacin has been previously reported as a potential cause of both hyper- and hypoglycemia, the exact mechanism is unknown. Several factors that may have been involved in our patient's hyperglycemia are discussed. She experienced hyperglycemic changes more rapidly than did the typical patients of previous reports. The Naranjo probability scale suggests a possible drug-related event. CONCLUSIONS: The temporal relationship between gatifloxacin administration and the patient's hyperglycemia suggests an iatrogenic cause. Based on our experience and the product labeling, clinicians should be more aware of the blood glucose-altering effects of gatifloxacin.     

Quantitative analysis of glucose loss during acute therapy for hyperglycemic hyperosmolar syndrome

Four patients with severe hyperglycemia and hyperosmolality were studied to quantitate the major mechanisms responsible for the fall in blood glucose concentration. Insulin was not administered to any of these patients during the first 15 h of therapy. In each case, there was a fall in glucose concentration due to dilution; this was quantitated by chloride space analysis and accounted for 24-34% of the fall in concentration. The size of the glucose pool decreased for two reasons. Glucosuria accounted for the majority of the reduction in the size of the glucose pool in the patients with the smallest decrease in extracellular fluid (ECF) volume [and hence the best preserved glomerular filtration rate (GFR)]. In contrast, glucosuria was a less important factor in causing glucose loss in the patients with very low GFR values. The size of the glucose pool also decreased due to glucose metabolism that did not require exogenous insulin. Thus the fall in glucose concentration in the initial therapy in patients with the hyperglycemic hyperosmolar syndrome is multifactorial and is not absolutely dependent on exogenous insulin. Furthermore, the patients grouped in this diagnostic category represent a heterogeneous population with the common features of severe hyperglycemia, hyperosmolality, and a negative or weakly reactive test for serum ketones.     

Effect of low-calorie parenteral nutrition on the incidence and severity of hyperglycemia in surgical patients: a randomized, controlled trial

OBJECTIVE: To determine the effect of a low-calorie parenteral nutrition (PN) regimen on the incidence and severity of hyperglycemia and insulin requirements. DESIGN: Prospective, randomized, clinical trial. SETTING: Urban, university-affiliated, level-I trauma center. PATIENTS: Consecutive surgical patients requiring PN. INTERVENTIONS: Patients were randomized to receive either a low-calorie PN formulation (20 nonprotein kilocalories per kg per day) or a standard PN formulation (30 nonprotein kilocalories per kg per day). Lipid-derived calories were standardized to 1000 kilocalories three times weekly for all patients; consequently, the number of calories varied only by the amount of carbohydrate administered. Protein requirements were individualized on the basis of estimated metabolic stress. Hyperglycemia was defined as a blood glucose level > or = 200 mg/dL. MEASUREMENTS AND MAIN RESULTS: Forty patients were evaluated (low-calorie PN, n = 20; standard PN, n = 20). Demographics of the two groups were similar. The incidence of hyperglycemic events was significantly lower in the low-calorie group (0% [0-0.5] vs. 33.1% [0-58.4]; p = .001]. Additionally, the severity of hyperglycemia was also lower in the low-calorie group (mean glucose area under the curve = 118 +/- 22 [mg x hr]/dL vs. 172 +/- 44 [mg x hr]/dL; p < .001). This resulted in lower average daily insulin requirements (0 [0-0] units vs. 10.9 [0-25.6] units; p < .001.). The only predictor of hyperglycemia was a dextrose administration rate >4 mg/kg/min. CONCLUSIONS:: Administration of a low-calorie PN formulation resulted in fewer and less-severe hyperglycemic events and lower insulin requirements. PN regimens should not exceed a dextrose administration rate of 4 mg/kg/min to avoid hyperglycemic events.     

Severe hyperglycemia during renally adjusted gatifloxacin therapy

OBJECTIVE: To report a case of severe hyperglycemia in a nondiabetic patient receiving gatifloxacin that was properly dosed based on renal function. CASE SUMMARY: A 65-year-old nondiabetic female with progressive renal dysfunction was admitted for severe hyperglycemia. The patient had received 9 days of a 10-day course of renally adjusted therapy with gatifloxacin 200 mg/day for bronchitis. Her blood glucose level on admission was 1121 mg/dL, at which point the gatifloxacin was discontinued. After several days of intensive insulin therapy, the blood glucose levels returned to normal, and the patient was subsequently discharged. DISCUSSION: Gatifloxacin-induced hyperglycemia has been reported in the literature, but based on a MEDLINE search (1966-December 2004), no such cases were found in a nondiabetic patient receiving the proper gatifloxacin dose, adjusted for degree of renal insufficiency. The available case reports seem to suggest the increase in blood glucose concentrations could have been precipitated by high drug concentrations in patients not receiving the renally adjusted dose or in those with preexisting, undiagnosed diabetes. A definite mechanism of action for gatifloxacin-induced hyperglycemia is not known. The Naranjo probability scale revealed a probable adverse reaction of hyperglycemia associated with gatifloxacin therapy. CONCLUSIONS: Healthcare professionals should be more aware of the possible development of hyperglycemia in all patients taking gatifloxacin, including those who are not diabetic and those receiving appropriately reduced doses for renal dysfunction.     

A case of successful treatment of a patient with hyperglycemia of 2700 mg/dL

A 34-year-old man with obesity who was an avid consumer of soft drinks was found in a coma after complaining of a poor physical condition for a few days. On arrival, he had hyperglycemia of 2700 mg/dL, coma, shock, sepsis, aspiration pneumonia, acute renal failure, acute pancreatitis, liver dysfunction, and systemic mycosis. The rapid infusion of a large volume of isotonic saline, insulin, antibiotics, and ulinastatin was performed, and mechanical ventilation was applied. The treatment was complicated by transient hypernatremia resulting from osmostasis, which gradually decreased. He demonstrated transient decerebrate posturing upon stimulation; however, he became conscious within a week of admission, and his associated diseases also improved. After correcting his hyperglycemia, the patient was discharged on foot. We report our case of a patient with hyperglycemia of 2700 mg/dL, which was the highest value reported in the English literature. During the correction of the hyperglycemia, transient hypernatremia occurred to prevent abrupt decrease in osmolality, which thus resulted in cell swelling.     

Insulin therapy for the critically ill patient

The risk of mortality or significant morbidity is high among critically ill patients who are treated in the intensive care unit (ICU) for > 5 days. These patients are susceptible to sepsis, excessive inflammation, critical illness polyneuropathy, and multiple organ failure, the latter often being the cause of death. Most intensive care patients, even those who did not previously suffer from diabetes, are hyperglycemic, which is presumed to reflect an adaptive development of insulin resistance. In the K.U. Leuven study it was hypothesized that hyperglycemia is not a beneficial adaptation to severe illness but rather predisposes patients to many of the typical intensive care complications--prolonged intensive care dependence and death. The effects of intensive insulin therapy to maintain normoglycemia during critical illness were studied in a large group (N = 1548) of ventilated, surgical ICU patients. An algorithm was proposed for implementing this procedure. The randomly assigned intensive insulin therapy group received insulin infusion tailored to control blood glucose (BG) levels in the range 80-110 mg/dL, whereas the conventional treatment group received insulin only when glucose levels exceeded 200 mg/dL, and in that event were maintained in a target range of 180-200 mg/dL. Intensive insulin therapy induced a 43% reduction of intensive care mortality risk (P = 0.036 after correction for interim analyses) and a 34% reduction of hospital mortality (P = 0.005). A reduced risk of severe infections by 46% (P = 0.003) was associated with a 35% reduction in prolonged (> 10 d) requirement for antibiotic therapy (P < 0.001). In addition, excessive inflammation was prevented. Logistic regression analysis indicated that control of BG levels, rather than insulin administration itself, likely explains the observed clinical benefits. Use of insulin infusion to maintain normoglycemia using a titration algorithm, at least in populations similar to those in the Leuven study, improves outcome. Further data are needed to establish the applicability of this strategy to other patient groups, such as those in a medical ICU and in general hospital care.     

Hyperosmolar hyperglycemic state

Hyperosmolar hyperglycemic state is a life-threatening emergency manifested by marked elevation of blood glucose, hyperosmolarity, and little or no ketosis. With the dramatic increase in the prevalence of type 2 diabetes and the aging population, this condition may be encountered more frequently by family physicians in the future. Although the precipitating causes are numerous, underlying infections are the most common. Other causes include certain medications, non-compliance, undiagnosed diabetes, substance abuse, and coexisting disease. Physical findings of hyperosmolar hyperglycemic state include those associated with profound dehydration and various neurologic symptoms such as coma. The first step of treatment involves careful monitoring of the patient and laboratory values. Vigorous correction of dehydration with the use of normal saline is critical, requiring an average of 9 L in 48 hours. After urine output has been established, potassium replacement should begin. Once fluid replacement has been initiated, insulin should be given as an initial bolus of 0.15 U per kg intravenously, followed by a drip of 0.1 U per kg per hour until the blood glucose level falls to between 250 and 300 mg per dL. Identification and treatment of the underlying and precipitating causes are necessary. It is important to monitor the patient for complications such as vascular occlusions (e.g., mesenteric artery occlusion, myocardial infarction, low-flow syndrome, and disseminated intravascular coagulopathy) and rhabdomyolysis. Finally, physicians should focus on preventing future episodes using patient education and instruction in self-monitoring.     

Pathophysiology and therapy of diabetic ketoacidosis and of non-ketoacidotic hyperosmolar diabetic coma

Metabolic derangements in diabetic coma are the sequelae of insulin deficiency. These defects are aggravated by the actions of insulin counteracting ("diabetogenic") hormones and hypertonic dehydration, which both impair insulin action. Conversely, it has been shown that hypo-osmolar rehydration of a hyperosmolar, severely hyperglycaemic diabetic patient reduces insulin resistance and restores biological responsiveness of previously dehydrated insulin-dependent tissues towards insulin. Thus treatment of diabetic coma requires appropriate fluid and electrolyte replacement as a life-saving emergency action alongside insulin replacement. The use of proper rehydration during the past decade might also explain the reported fall in the insulin requirement for the treatment of diabetic coma from approximately 1,000 units per coma to low-dose insulin therapy. In order to guarantee proper treatment of severe hyperglycaemia and normalization of the hyperosmolar state, we feel that hypo-osmolar rehydration has to be initiated in parallel with low-dose insulin therapy (5 to 6 U/h) to restore the physiological response of the respective target tissues to insulin action and to ameliorate glucose utilization. This approach probably avoids a too rapid fall in plasma osmolarity, minimizes the risk of cerebral oedema and hypokalaemia, and improves survival. The development of severe diabetic ketoacidosis or of hyperosmolar non-ketotic diabetic coma should be prevented by advice to patients on the importance of metabolic monitoring, which can be done by proper self-monitoring of blood glucose. In addition, information should be provided on the detrimental metabolic effects of both dehydration and stress.     

Weakness, neuropathy, and coma following total parenteral nutrition in underfed or starved rats: relationship to blood hyperosmolarity and brain water loss.

The continuous infusion of a concentrated, high-caloric glucose solution intravenously into underfed or 3-day-starved rats at a rate of 390 kcal/kg/day results in hypophosphatemia, muscular weakness, neuropathy, lethargy, occasional convulsions, and eventual coma and death. This sequence of events is not observed in similarly infused normal rats. It is a model of a fatal parenteral nutrition syndrome which occurs in undernourished patients. Rats in coma had an eightfold increase in the blood glucose level, a 1.6-fold increase in serum osmolarity, a 16% to 20( decrease in brain water content, and normal blood ketones. A lag phase of at least 8 hr and often 12 to 24 hr occurred following the start of the hyperosmotic glucose infusion before the blood glucose began to accumulate progressively and the syndrome developed. The onset of the syndrome could be prevented by the administration of large amounts of insulin required to keep the blood sugar from exceeding 250 mg/dl. Thus the rat model of the fatal hyperalimentation syndrome is a form of hyperglycemic, hyperosmolar, nonketotic coma caused by brain dehydration.     

Challenges in hyperglycemia management in critically ill patients with COVID-19

Hyperglycemia is commonly associated with adverse outcomes especially in patients requiring intensive care unit stay. Data from the corona virus disease 2019 (COVID-19) pandemic indicates that individuals with diabetes appear to be at similar risk for COVID-19 infection to those without diabetes but are more likely to experience increased morbidity and mortality. The proposed hypothesis for hyperglycemia in COVID-19 include insulin resistance, critical illness hyperglycemia (stress- induced hyperglycemia) secondary to high levels of hormones like cortisol and catecholamines that counteract insulin action, acute cytokine storm and pancreatic cell dysfunction. Diabetic patients are more likely to have severe hyperglycemic complications including diabetic ketoacidosis and hyperosmolar hyperglycemic state. Management of hyperglycemia in COVID-19 is often complicated by use of steroids, prolonged total parenteral or enteral nutrition, frequent acute hyperglycemic events, and restrictions with fluid management due to acute respiratory distress syndrome. While managing hyperglycemia special attention should be paid to mode of insulin delivery, frequency of glucose monitoring based on patient and caregiver safety thereby minimizing exposure and conserving personal protective equipment. In this article we describe the pathophysiology of hyperglycemia, challenges encountered in managing hyperglycemia, and review some potential solutions to address them.     

Insulin use in NIDDM

The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms for an atherogenic action of insulin exist, current evidence does not prove cause and effect and does not warrant withholding insulin therapy (or compromising on dosage) when it is needed.     

食管癌术后并发高血糖高渗性非酮症性昏迷的临床分析

目的:探讨食管癌患者术后并发高血糖高渗性非酮症性昏迷的病因及临床防治策略。方法:回顾性分析2009年1月至2014年12月复旦大学附属中山医院胸外科收治的食管癌术后发生高血糖高渗性非酮症性昏迷的5例患者的临床资料。结果:5例患者术前均无糖尿病,术后均采用肠内营养,其中4例发生并发症。5例患者均以脱水、精神障碍为主要临床表现,严重者出现昏迷。3例发现早,及时处理后恢复较好,平均住院时间42 d,均痊愈;2例发现较晚,1例于术后第54天治疗无效死亡,1例住院时间长达210 d。所有患者均未发展为糖尿病。结论:非糖尿病的食管癌患者术后亦可发生高血糖高渗性非酮症性昏迷,在有并发症或使用肠内高营养的患者中较易发生,术后监测血糖可避免此并发症发生;早诊早治能改善此并发症的预后。     

Life-threatening hyperglycemia and acidosis related to olanzapine: a case report and review of the literature

The authors report a case with life-threatening hyperglycemia and acidosis in a patient with no previous diabetic history following treatment with olanzapine. A 35-year-old woman with a history of bipolar affective disorder treated with olanzapine presented with severe diabetic ketoacidosis. She had no prior history of diabetes or risk factors for diabetes. Glycosylated hemoglobin (HbA1c) on admission blood sample suggested that long-term glycemic control had been poor. The authors postulate that treatment with olanzapine precipitated hyperglycemia, an elevated creatine kinase level, and a high amylase level. A concurrent urinary tract infection precipitated an episode of sepsis, which combined to precipitate life-threatening diabetic ketoacidosis. During her stay in the intensive treatment unit and subsequently in the medical ward, her blood glucose concentration was intensively monitored. She remains on insulin therapy, and her antipsychotic medication was changed to risperidone. Newer atypical antipsychotic drugs such as olanzapine have been introduced with the benefit of fewer extrapyramidal side effects. A number of these have reported metabolic side effects of uncertain etiology such as diabetic ketoacidosis and elevated creatine kinase. The authors believe that the diabetic ketoacidosis occurred in this patient, who had no previous history of diabetes mellitus. Blood glucose should be monitored in patients taking olanzapine, especially in those patients with risk factors for diabetes mellitus.     

Control of insulin secretion during fasting hyperglycemia in adult diabetics and in nondiabetic subjects during infusion of glucose

In obese adult diabetics, the concentration of insulin in venous plasma was unrelated to the degree of hyperglycemia after an overnight fast. However, in these subjects, insulin rose and fell in proportion to the magnitude of change in plasma glucose induced by small intravenous infusions of glucose. The minimal dose of glucose to cause a significant rise in insulin above the fasting level was similar in normal subjects, obese nondiabetic subjects, and in obese, hyperglycemic adult diabetics. This dose lay between infusion of 60 and 100 mg of glucose per min for 30 min. These results suggested that the secretion of insulin was under regulation by changes in blood glucose but was not stimulated in proportion to the stable raised blood glucose concentration of the hyperglycemic diabetic. Artificial hyperglycemia was induced in fasting normal subjects by constant intravenous infusion of glucose at rates of 100-250 mg of glucose per min for periods up to 8 hr. Plasma glucose rose during the 1st hr of infusion and then remained constantly elevated for up to 8 hr. The concentration of plasma insulin paralleled that of plasma glucose. During the period of constant hyperglycemia and elevated insulin, superimposition of a brief additional glucose load resulted in a prompt rise in glucose and insulin, both returning to the previous elevated levels.Thus in normals as well as obese diabetics, stable hyperglycemia does not produce a pancreatic response sufficient to return the blood glucose to an arbitrary normal fasting concentration, yet the beta cells remain readily responsive to a change in plasma glucose. These data suggest that the beta cells do not operate as a control system with an absolute reference point when presented with systemic hyperglycemia. The behavior of the beta cells during hyperglycemia in the fasting obese adult diabetic suggests that the regulation of the basal insulin secretion may not be determined by factors directly related to the prevailing concentration of glucose. It is postulated that the beta cells adapt to hyperglycemia perhaps through the operation of controls directed toward a normal delivery of free fatty acids or some other cellular metabolic substrate during fasting.