Insulin tolerance test causes hypokalaemia and can provoke cardiac arrhythmias

We report the observation and analysis of a new adverse event during the insulin tolerance test (ITT) and propose additional safety procedures. An 8-year-old girl with growth hormone insufficiency had a cardiac arrest due to ventricular flutter when she was tested for growth hormone deficiency by the ITT. Severe hypokalaemia (K+ 2.6 mmol/l) was observed after resuscitation. Ergometry ECG revealed catecholaminergic polymorphic ventricular tachycardia, a hereditary arrhythmogenic disease. Consecutive measurements of serum potassium during ITT in 29 short children (21 boys) with growth failure revealed a mean decrease of serum potassium by 1.1 +/- 0.4 mmol/l with the nadir at 30 min after the insulin bolus. Hypokalaemia (serum potassium < 3.5 mmol/l) occurred in all but one child; severe hypokalaemia (serum potassium < 2.9 mmol/l) was measured in every third child. This observation indicates that acute hypokalaemia which is induced by insulin and catecholamine excess occurs frequently in ITT. The case shows that the combination of acute hypokalaemia and the adrenergic counterregulation in ITT is a strong trigger of cardiac arrhythmias, which can become life-threatening if the child has an arrhythmogenic disease. Therefore, we recommend ECG monitoring during ITT to enhance the detection of cardiac arrhythmias. In addition, in the case of a comatose child during ITT the determination of the glucose and potassium level as well as adequate treatment are necessary.     

Management of severely brittle diabetes by continuous subcutaneous and intramuscular insulin infusions: evidence for a defect in subcutaneous insulin absorption.

Severely brittle diabetes is defined as a rare subtype of insulin-dependent diabetes with wide, fast, unpredictable, and inexplicable swings in blood glucose concentration, often culminating in ketoacidosis or hypoglycaemic coma. To assess the role of inappropriate type, amount, or timing of insulin treatment and the route of administration as a cause of severe brittleness six patients with continuous subcutaneous insulin infusion, which provides a high degree of optimisation of dosage with exogenous insulin in stable diabetics. The glycaemic control achieved during continuous subcutaneous insulin infusion was compared with that during continuous intramuscular insulin infusion. Six patients with non-brittle diabetes were also treated by continuous subcutaneous insulin infusion. These patients achieved the expected improvement in glycaemic control (mean +/- SD plasma glucose concentration 5.1 +/- 2.3 mmol/l (92 +/- 41 mg/100 ml)), but not the patients with brittle diabetes remained uncontrolled with continuous subcutaneous infusion (13.6 +/- 5.8 mmol/1 (245 +/- 105 mg/100 ml) compared with 10.3 +/- 4.1 mmol/l (186 +/- 74 mg/100 ml) during treatment with optimised conventional subcutaneous injections). During continuous intramuscular infusion, however, glycaemic control in five of the patients with brittle diabetes was significantly improved (7.7 +/- 2.6 mmol/l (139 +/- 47 mg/100 ml). The remaining patient with brittle diabetes, previously safely controlled only with continuous intravenous insulin, did not respond to continuous intramuscular infusion. It is concluded that in five of the six patients with brittle diabetes studied here impaired or irregular absorption of insulin from the subcutaneous site played a more important part in their hyperlability than inappropriate injection strategies. This absorption defect was presumably bypassed by the intramuscular route.     

Hypokalemia during the treatment of arterial hypertension with diuretics.

In a study of 50 patients with uncomplicated arterial hypertension the administration of hydrochlorothiazide, 50 to 100 mg daily or every other day, with or without reserpine, 0.25 mg daily, resulted in a fall in the mean blood pressure from 182/113 to 144/92 mm Hg. The mean duration of therapy was 19 months. The mean serum potassium concentration was 4.3 mmol/l before the onset of therapy. It fell during the first 6 weeks of treatment, but seldom below 3.5 mmol/l, then rose gradually and spontaneously to 4.1 mmol/l after 19 months of therapy. All the patients remained asymptomatic. These findings bring into question the routine use of potassium supplements or a potassium-sparing diuretic, such as spironolactone or triamterene, during the treatment of hypertension with diuretics such as the thiazides. The use of potassium supplements or a potassium-sparing agent may induce hyperkalemia in spite of the simultaneous administration of a diuretic that acts more proximally. Since hyperkalemia is potentially lethal, the serum potassium concentration should be carefully monitored in any patient receiving potassium supplements or a potassium-sparing agent.     

Selected developments in the understanding of diabetic ketoacidosis.

Advances in the understanding of diabetic ketoacidosis have contributed to the recent decrease in the morbidity and mortality associated with this condition. The role of counterregulatory hormones in its pathogenesis is considerable, but insulin deficiency is necessary for diabetic ketoacidosis to develop. Therapy begins with identification and treatment of the factors precipitating ketosis. Isotonic saline is the fluid of choice for initial intravenous therapy; subsequently 0.45% saline is appropriate. Sodium bicarbonate is necessary only if the arterial pH is less than 7.1, and phosphate should be given only when the serum phosphate level is below 0.5 mg/dl (0.16 mmol/l). Factors other than pH are important in causing the hyperkalemia so commonly seen at the time of presentation, but whether or not hyperkalemia is present potassium supplementation is almost always necessary and should be given as long as the urinary output is adequate. Intravenous doses of insulin as low as 5 to 15 U/h are sufficient in most cases, but the occasional patient will require larger amounts. Close clinical and biochemical monitoring is necessary for successful management.     

Fulminant Type 1 diabetes in a pregnant woman as an initial manifestation of the insulin autoimmune syndrome

Diabet. Med. 29, 1335-1338 (2012) ABSTRACT: Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (相似文献   

Role of residual insulin secretion in protecting against ketoacidosis in insulin-dependent diabetes.

The role of preserved beta-cell function in preventing ketoacidosis in type I insulin-dependent diabetes was assessed in eight patients with and seven patients without residual beta-cell function as determined from C-peptide concentrations. After 12 hours of insulin fatty-acid, and glycerol concentrations were all significantly higher in patients without beta-cell function than in those with residual secretion. Mean blood glucose concentrations reached 17.2 +/- SE of mean 1.3 mmol/l (310 +/- 23 mg/100 ml) in the first group compared with 8.8 +/- 1.4 mmol/l (159 +/- 25 mg/100 ml) in the second (P less than 0.01), while 3-hydroxybutyrate concentrations rose to 5.5 +/- mmol/l (57 +/- 5 mg/100 ml) and 1.4 +/- 0.3 mmol/l (15 +/- 3 mg/100 ml) in the two groups respectively (P less than 0.01). Individual mean C-peptide concentrations showed a significant inverse correlation with the final blood glucose values (r = -0.91; P less than 0.02). These findings strongly suggest that even minimal residual insulin secretion is important for metabolic wellbeing in diabetes and may prevent the development of severe ketoacidosis when insulin delivery is inadequate.     

Profound Hypokalemia in Diabetic Ketoacidosis: A Therapeutic Challenge

ObjectiveTo describe profound hypokalemia in a comatose patient with diabetic ketoacidosis.MethodsWe present a case report, review the mechanisms for the occurrence of hypokalemia in diabetic ketoacidosis, and discuss its management in the setting of hyperglycemia and hyperosmolality.ResultsA 22-year-old woman with a history of type 1 diabetes mellitus was admitted in a comatose state. Laboratory tests revealed a blood glucose level of 747 mg/dL, serum potassium of 1.9 mEq/L, pH of 6.8, and calculated effective serum osmolality of 320 mOsm/kg. She was intubated and resuscitated with intravenously administered fluids. Intravenous administration of vasopressors was necessary for stabilization of the blood pressure. Intravenous infusion of insulin was initiated to control the hyperglycemia, and repletion of total body potassium stores was undertaken. A total of 660 mEq of potassium was administered intravenously during the first 12.5 hours. Despite such aggressive initial repletion of potassium, the patient required 40 to 80 mEq of potassium daily for the next 8 days to increase the serum potassium concentration to normal.ConclusionProfound hypokalemia, an uncommon initial manifestation in patients with diabetic ketoacidosis, is indicative of severe total body potassium deficiency. Under such circumstances, aggressive potassium repletion in a comatose patient must be undertaken during correction of other metabolic abnormalities, including hyperglycemia and hyperosmolality. Intravenously administered insulin should be withheld until the serum potassium concentration is ≥ 3.3 mEq/L. (Endocr Pract. 2005;11:331-334)     

Hypothermia: a complication of diabetic ketoacidosis.

During 1969-77, 20 episodes of severe hypothermia occurred in 19 diabetic patients in Nottingham. Thirteen were associated with ketotic hyperosmolar coma, two with lactic acidosis, and one with hypoglycaemia, while in four there was no loss of diabetic control. Ketoacidosis accounted for 11.8% of all admissions for severe accidental hypothermia and was a commoner cause than hypothyroidism (8%). Patients with ketoacidosis were younger and developed hypothermia as often during the summer as during the winter. The metabolic disturbance was characteristic, with severe acidosis (mean pH 7.04), a high blood glucose concentration (mean 56.6 mmol/l; 1020 mg/100 ml), and high plasma osmolality (mean 379.7 mmol (mosmol)/kg). Eight of the 13 episodes proved fatal. Hypothermia may aggravate ketoacidosis and complicate treatment and should be sought in all patients with severe diabetic coma.     

Effects of octreotide on lipid metabolism in acromegaly.

Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.     

Effects of human diabetic serum on the in vitro development of early somite rat embryos

High levels of glucose, beta-hydroxybutyrate (B-HOB), and acetoacetate are known to have embryotoxic and teratogenic effects on rat embryos in culture, especially when added concomitantly to the culture medium. We studied the effects of human serum from different types of diabetes mellitus on the in vitro development of 10 1/2-day-old rat embryos cultured for 48 hours. We used serum from type I diabetes with and without ketoacidosis and type II diabetes either untreated or treated with insulin or with daonil. Type I diabetes without ketoacidosis increased the rate of malformations to 27% vs. 11% in controls. Serum from type I diabetes with ketoacidosis further increased the malformation rate to 44%. The rate of malformations induced by serum of type II diabetes was dependent on the treatment. It was relatively low among embryos cultured on serum from untreated (16%) or treated with daonil (19%) and rose to 27% among embryos cultured on serum from type II diabetes treated with insulin. No significant correlation was found between the rate of malformations and the concentrations of glucose, B-HOB, acetoacetate, and HbA1c in all diabetic sera except serum from type I diabetes with ketoacidosis. We may therefore conclude that for most types of diabetes in humans, neither the high blood glucose concentrations nor the high levels of ketone bodies seem to be the main reason for the high rate of malformations. However, we used cultured rat embryos, and the effects on the human embryo may be different. The results of studies on various experimental animal models in diabetes teratogenicity seem to have only partial relevance to the human situation.     

Hypokalaemia and diuretics: an analysis of publications.

Published data have been used to define the characteristics of the fall in serum potassium concentration after taking diuretics and the efficacy of the various treatments given to prevent or correct it. The average fall is less after the usual doses of frusemide (about 0.3 mmol/l) than after the usual doses of thiazides (about 0.6 mmol/l) and is little influenced by the dose or duration of treatment. The fall with a given drug is the same in heart failure and hypertension, but the initial serum potassium concentration is higher in heart failure, so that the final value is lower in hypertension. In standard doses potassium supplements are less effective than potassium-retaining diuretics in correcting the hypokalaemia. The relation between the average serum potassium value and the frequency of low values (hypokalaemia) is such that very low values after taking diuretics are unusual in patients with hypertension or heart failure. Hypokalaemia would almost disappear as an important complication of diuretic treatment if it was defined as a value less than 3.0 mmol/l rather than as a value less than 3.5 mmol/l.     

Carrier solutions for low-level intravenous insulin infusion.

In the use of low-level intravenous insulin infusion for treating diabetic hyperglycaemia and ketoacidosis adsorption of insulin to containers or plastic infusion apparatus results in significant losses of 60-80% of insulin in dilute physiological saline solution (40 U/l). It is therefore necessary to add protein to the carrier solution to minimize losses and maintain a constant delivery rate. Recovery studies showed that 3.5% w/v polygeline solution (polymer of degraded gelatin) was a suitable medium for this purpose, offering some advantages over human serum albumin. A minimum concentration of 0.5% polygeline was required to ensure adequate delivery of insulin to the patient.     

Comparison of high fibre diets,basal insulin supplements,and flexible insulin treatment for non-insulin dependent (type II) diabetics poorly controlled with sulphonylureas.

OBJECTIVE--To compare high fibre diet, basal insulin supplements and a regimen of insulin four times daily in non-insulin dependent (type II) diabetic patients who were poorly controlled with sulphonylureas. DESIGN--Run in period lasting 2-3 months during which self monitoring of glucose concentration was taught, followed by six months on a high fibre diet, followed by six months'' treatment with insulin in those patients who did not respond to the high fibre diet. SETTING--Teaching hospital diabetic clinics. PATIENTS--33 patients who had had diabetes for at least two years and had haemoglobin A1 concentrations over 10% despite receiving nearly maximum doses of oral hypoglycaemic agents. No absolute indications for treatment with insulin. INTERVENTIONS--During the high fibre diet daily fibre intake was increased by a mean of 16 g (95% confidence interval 12 to 20 g.) Twenty five patients were then started on once daily insulin. After three months 14 patients were started on four injections of insulin daily. ENDPOINT--Control of diabetes (haemoglobin A1 concentration less than or equal to 10% and fasting plasma glucose concentration less than or equal to 6 mmol/l) or completion of six months on insulin treatment. MEASUREMENTS AND MAIN RESULTS-- No change in weight, diet, or concentrations of fasting glucose or haemoglobin A1 occurred during run in period. During high fibre diet there were no changes in haemoglobin A1 concentrations, but mean fasting glucose concentrations rose by 1.7 mmol/l (95% confidence interval 0.9 to 2.5, p less than 0.01). With once daily insulin mean concentrations of fasting plasma glucose fell from 12.6 to 7.6 mmol/l (p less than 0.001) and haemoglobin A1 from 14.6% to 11.2% (p less than 0.001). With insulin four times daily concentrations of haemoglobin A1 fell from 11.5% to 9.6% (p less than 0.02). Lipid concentrations were unchanged by high fibre diet. In patients receiving insulin the mean cholesterol concentrations fell from 7.1 to 6.4 mmol/l (p less than 0.0001), high density lipoprotein concentrations rose from 1.1 to 1.29 mmol/l (p less than 0.01), and triglyceride concentrations fell from 2.67 to 1.86 mmol/l (p less than 0.05). Patients taking insulin gained weight and those taking it four times daily gained an average of 4.2 kg. CONCLUSIONS--High fibre diets worsen control of diabetes in patients who are poorly controlled with oral hypoglycaemic agents. Maximum improvements in control of diabetes were achieved by taking insulin four times daily.     

Increased incidence of true type I diabetes acquired during pregnancy.

A longitudinal study was carried out of all patients with newly acquired insulin dependent diabetes during pregnancy (as distinct from non-insulin-dependent gestational diabetes) seen at the Copenhagen Centre for Diabetes and Pregnancy during 1966 to 1980. The series comprised 63 patients with a mean age of 27 (SEM 1) years. At diagnosis the mean fasting blood glucose concentration was 15.6 (1.3) mmol/l and mean maximal insulin dose 49 (3) IU/day. At a prospective follow up examination a mean of 8 (SEM 1) years after diagnosis 46 of 60 patients (77%) were being treated with insulin (35 (2) IU/day) and had a very low mean stimulated plasma C peptide value (0.12 (0.02) nmol/l) suggesting absent or nearly absent beta cell function. The remaining 14 patients (23%), not currently receiving insulin, appeared to be severely glucose intolerant, having a mean fasting blood glucose concentration of 13.4 (1.2) mmol/l. Thus most of these patients developing insulin dependent diabetes during pregnancy had true type I disease. Compared with the age specific incidence of type I diabetes in the background population of women the incidence was at least 70% higher in pregnant than non-pregnant women (p less than 0.001; chi 2 = 11.6; f = 1). This increased incidence occurred in the third trimester when the risk of developing type I diabetes was 3.8 times that of non-pregnant women (p less than 0.000001; chi 2 = 35.6; f = 1). Finally, the risk of developing insulin dependent diabetes during pregnancy was lower when conception occurred in the winter (p less than 0.05; chi 2 = 4.18; f = 1).     

血必净注射液联合静脉胰岛素泵入治疗糖尿病酮症酸中毒的效果及对氧化应激反应的影响

目的:探讨血必净注射液联合静脉胰岛素泵入治疗糖尿病酮症酸中毒的效果及对氧化应激反应的影响。方法:选择2016年8月至2018年8月我院收治的糖尿病酮症酸中毒患者80例,根据随机数表法分为观察组(n=41)和对照组(n=39)。对照组给予胰岛素泵治疗,观察组在对照组的基础上采用血必净注射液治疗。比较两组患者的临床疗效、治疗前后单核细胞趋化蛋白(MCP)、空腹血糖(FBG)、餐后血糖(PBG)、丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(TAC)水平的变化及临床症状改善时间。结果:治疗后,两组单核细胞趋化蛋白水平均较治疗前显著下降,且观察组明显低于对照组(P0.05)。治疗后,观察组MDA低于对照组,SOD、TAC水平均显著高于对照组(P0.05);观察组血糖达标、尿酮体转阴、PH恢复时间及胰岛素用量均显著低于对照组(P0.05)。结论:血必净注射液联合胰岛素泵治疗糖尿病酮症酸中毒患者的效果显著明显优于单用血必净治疗,可能与其有效提高机体的抗氧化能力有关。     

Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis.

The effect of intravenous bicarbonate on the changes in intermediary metabolites during the initial treatment of diabetic ketoacidosis was examined in 16 patients. The results were compared with the changes seen in 16 patients receiving intravenous saline. Infusion of 150 mmol (mEq) bicarbonate significantly delayed the fall in blood lactate, lactate:pyruvate ratio, and total ketone bodies observed in the saline treated group. No difference in the rate of fall of blood glucose concentration was found. There is no metabolic indication for the use of intravenous bicarbonate in the treatment of diabetic ketoacidosis.     

Nocturnal hypoglycaemia in patients receiving conventional treatment with insulin.

The prevalence of nocturnal biochemical hypoglycaemia--that is, blood glucose concentrations below 3 mmol/l (55 mg/100 ml)--was evaluated in a random sample of 58 insulin dependent diabetics receiving twice daily insulin. Seventeen patients had at least one blood glucose value below 3 mmol/l (55 mg/100 ml) and five a value below 2 mmol/l (36 mg/100 ml) during the night. Both bedtime (2300) and fasting morning (0700) blood glucose concentrations were significantly lower in the group with nocturnal hypoglycaemia compared with the group without (p less than 0.00001). If the bedtime blood glucose concentration was below 6 mmol/l (108 mg/100 ml) the risk of nocturnal hypoglycaemia was 80% (95% confidence limits 51-96%). If the bedtime blood glucose concentration was above 6 mmol/l the likelihood of hypoglycaemia not occurring during the night was 88% (74-96%). The mean glycosylated haemoglobin A1c (HbA1c) concentration in the group with nocturnal biochemical hypoglycaemia (8.2 (range 5.0-12.4)%) was significantly lower than that in the group without (9.4(7.0-14.2)%) (p less than 0.02). The prevalence of nocturnal hypoglycaemia in the patients receiving twice daily insulin (29%) was compared with that in 15 patients receiving thrice daily insulin (47%) and was not found to be significantly different. The likelihood of this risk being greater with thrice daily insulin was, however, 88%. No patient with nocturnal biochemical hypoglycaemia woke up during the night with symptomatic hypoglycaemia. Nocturnal biochemical hypoglycaemia is common during twice daily treatment with insulin, and low values of HbA1c might be associated with a higher risk of such hypoglycaemia. The blood glucose concentration at bedtime is a significant predictor of nocturnal biochemical hypoglycaemia, and HbA1c values might be of help in identifying patients at risk.     

Autoimmune insulin syndrome in a patient with progressive systemic sclerosis receiving penicillamine.

The case of a patient with progressive systemic sclerosis, who developed hypoglycaemia and insulin autoantibodies, is described. Repeated blood glucose measurements showed levels less than 2.8 mmol/l. High immunoreactive insulin levels, with undetectable free insulin, led to the discovery of anti-insulin antibodies in the patient's serum. He had no history of exogenous insulin use and was receiving penicillamine treatment. A double mechanism for the autoimmune insulin syndrome in this case is proposed: acting in a patient with increased humoral immunoresponsiveness, penicillamine might have induced the development of insulin autoantibodies.     

Brittle diabetes: long-term control with a portable,continuous, intravenous insulin infusion system.

A young woman had severe brittle diabetes mellitus that was critically unmanageable with all conventional insulin treatment. Continuous subcutaneous and intramuscular infusions of insulin also failed to control her metabolic instability. Use of a continuous intravenous infusion, however, whereby a portable, variable-rate, battery-operated syringe pump delivered insulin through a subcutaneously tunnelled central venous catheter, resulted in good control. When she was receiving hourly intramuscular insulin injections (a mean of 778 IU daily) mean blood glucose concentrations had been 22.1 +/- 1.4 mmol/l (398 +/- 25 mg/100 microliters). After she had received the intravenous infusion for one month as an outpatient mean blood glucose concentration was 8.2 +/- 0.46 mmol/l (148 +/- 8 mg/100 microliters) and only 80 IU insulin daily was required. Follow-up after over five months of use showed that few complications had occurred. The system is simple to use and safe, and the diabetes had been stabilised such that she could enjoy a near-normal life style.     

Relationship between the concentration of H+-ions and the efficiency of insulin in the treatment of diabetic ketoacidosis

The efficiency of insulin (decrease of the blood glucose per unit of insulin administered) was assessed in 610 cases of diabetic ketoacidosis (316 females, 274 males, aged 3 to 72 years) in terms of the degree of plasma acidemia. The 610 cases were grouped into 4 ketoacidosis stages, defined according to pH values as incipient, pH > 7.35 (77 cases); moderate, pH 7.31-7.35 (163 cases); advanced, 7.21-7.30 (160 cases); severe, pH < 7.20 (210 cases). The mean [H+]-ion concentration recorded on admission in the 4 stages of ketoacidosis was 41 nEq/1, 46 nEq/1, 53 nEq/1, and 91 nEq/1, respectively. The efficiency of insulin for the first 2 hours of treatment (interval during which acidemia was only partly corrected) was comparable in the four ketoacidosis stages, i.e. 31.1 mg/l, 32.9 mg/l, 29.5 mg/l and, respectively 28.9 mg/l per unit of insulin injected as a bolus. The somewhat lower efficiency of insulin in the advanced and severe cases of ketoacidosis appears to be due to vascular collapse encountered in 38 cases (6 advanced ketoacidosis and 32 severe ketoacidosis), since in these patients the fall in blood glucose per unit insulin was only 15.8 mg/l.