Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome after renal transplantation in the United States

BACKGROUND: The incidence and risk factors for diabetic ketoacidosis (diabetic ketoacidosis) and hyperglycemic hyperosmolar syndrome (hyperglycemic hyperosmolar syndrome, previously called non-ketotic hyperosmolar coma) have not been reported in a national population of renal transplant (renal transplantation) recipients. METHODS: We performed a historical cohort study of 39,628 renal transplantation recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998, followed until 31 Dec 1999. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (ICD-9 code 250.1x) and hyperglycemic hyperosmolar syndrome (code 250.2x). Cox Regression analysis was used to calculate adjusted hazard ratios for time to hospitalization for diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. RESULTS: The incidence of diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were 33.2/1000 person years (PY) and 2.7/1000 PY respectively for recipients with a prior diagnosis of diabetes mellitus (DM), and 2.0/1000 PY and 1.1/1000 PY in patients without DM. In Cox Regression analysis, African Americans (AHR, 2.71, 95 %CI, 1.96-3.75), females, recipients of cadaver kidneys, patients age 33-44 (vs. >55), more recent year of transplant, and patients with maintenance TAC (tacrolimus, vs. cyclosporine) had significantly higher risk of diabetic ketoacidosis. However, the rate of diabetic ketoacidosis decreased more over time in TAC users than overall. Risk factors for hyperglycemic hyperosmolar syndrome were similar except for the significance of positive recipient hepatitis C serology and non-significance of female gender. Both diabetic ketoacidosis (AHR, 2.44, 95% CI, 2.10-2.85, p < 0.0001) and hyperglycemic hyperosmolar syndrome (AHR 1.87, 95% CI, 1.22-2.88, p = 0.004) were independently associated with increased mortality. CONCLUSIONS: We conclude that diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were associated with increased risk of mortality and were not uncommon after renal transplantation. High-risk groups were identified.     

糖尿病患者外科手术麻醉的临床研究与探讨

目的:研究与探讨糖尿病患者外科手术麻醉的安全性和有效性。方法:糖尿病外科手术患者262例。其中急性胆囊炎64例,胃穿孔52例,化脓性阑尾炎71例,阑尾穿孔弥漫性腹膜炎各63例,外伤性脾破裂12例。采用硬膜外麻醉146例,全身麻醉116例。结果:所有患者均手术顺利,麻醉平稳,麻醉手术过程中血糖水平较术前均有不同程度升高,按升高的血糖量适当增加胰岛素用量,血糖控制在10-12mmol/L,尿酮体(-),无糖尿病酮症酸中毒、高渗性非酮症性高血糖昏迷及低糖症发生。术毕均及时清醒,拔管,血糖水平较平稳。结论:急诊糖尿病患者手术时采用硬膜外麻醉对血糖影响小于全麻。     

Suppressive effect of vasopressin on ketosis in diabetic rats.

In order to clarify if vasopressin (VP) plays a role in the pathophysiology of hyperosmolar nonketotic diabetic coma (HNDC), VP has been infused to diabetic rats and plasma levels of glucose (PG), ketone bodies, FFA and glucagon were determined. High-dose VP infusion (1.2 U/kg/h) caused gradual elevation of PG (60%) and glucagon levels (600%), while ketone bodies showed transient decrease (20%) at 30 min. Under the suppression of endogenous glucagon secretion by constant infusion of somatostatin (100 micrograms/kg/h), high dose VP showed 25% increase in PG levels and 30% reduction of ketone body levels for the subsequent VP infusion for 1.5 hour. Low-dose VP infusion (0.06 U/kg/h) had no hyperglycemic effect, but suppressed ketosis (20%) in the same condition. There were no changes in plasma FFA concentrations, indicating no significant effect of VP on lipolysis. The results indicate that VP often elevated in HNDC may play an important role for the pathophysiology of HNDC through suppression of hepatic ketogenesis.     

Diabetic Ketoacidosis—A Review of Cases at a University Medical Center

Twenty-five cases of diabetic ketoacidosis were studied retrospectively with respect to clinical characteristics and results of therapy. In this series (as with all 88 patients admitted in the last five years with a diagnosis of diabetic ketoacidosis) there were no deaths. Infection was found to be the most common precipitating event, documented by physical findings and cultures in one-third of these cases.In about two-thirds of the cases, electrocardiograms which were read as abnormal on admission reverted to normal after therapy.In all patients serum potassium levels decreased from admission values; one patient became symptomatically hypokalemic.Low serum potassium levels on admission and early vigorous bicarbonate therapy are emphasized as major predisposing factors of symptomatic hypokalemia. None of the patients had overt hyperosmolar coma, lactic acidosis or cerebral edema during therapy.     

Hyperosmolar Non-ketotic Diabetic Coma: With Particular Reference to Vascular Complications

Two West Indian men with no previous history of diabetes mellitus developed hyperosmolar non-ketotic diabetic coma. Intra-abdominal catastrophes secondary to mesenteric thrombosis played a major part in the death of these patients, in both of whom control of the hyperosmolar state had been achieved. Both patients had evidence of infarction of intestine at necropsy. Vascular thromboses are a major complication of this form of coma and must be considered when such patients develop signs of an acute abdomen.     

Lactic Acidosis in Diabetes

Lactic acidosis is occasionally responsible for metabolic acidosis in diabetics. It may occur in the presence of normal blood levels of the ketone bodies, and such cases are often described as having “non-ketotic diabetic acidosis.” Lactic acid may contribute to the metabolic acidosis in patients with true diabetic ketoacidosis, but the blood lactate concentrations in these patients are not usually very high. In some patients the ketoacidosis is replaced by a lactic acidosis during treatment. This usually occurs in association with a serious underlying disorder and is associated with a poor prognosis. A transient increase in blood lactate concentration was in fact observed in most patients after the beginning of treatment, but the significance of this finding is uncertain.     

Decreased ketonaemia in the monosodium glutamate-induced obese rats

Plasma concentrations of total ketone bodies, acetoacetate (AcAc) and 3-hydroxybutyrate (3-OHBA) in monosodium glutamate (MSG)-induced obese rats were measured. MSG-treated rats showed higher Lee's indices, shorter naso-anal and tail length, and a more marked intraperitoneal fat deposition than control rats. Plasma concentrations of glucose, free fatty acid, triglyceride and phospholipids were significantly increased in the MSG-treated rats as compared to the control rats (24 weeks-old). Plasma levels of total ketone bodies, AcAc and 3-OHBA were all decreased in the MSG-treated rats as compared to control rats. The ratio, 3-OHBA/AcAc in the MSG-treated rats were not different from those in the control rats.     

The effects of 3-hydroxybutyrate and glucose on human T cell responses to Candida albicans

Abstract Diabetic patients are particularly susceptible to mucocutaneous candidosis. T lymphocytes are central to the induction of antigen-specific immune responses and may be sensitive to the biochemical abnormalities associated with poorly controlled diabetes; namely, hyperglycaemia and/or ketonemia. To examine this we have studied the effect of varying concentrations of glucose and 3-hydroxybutyrate (3-HB) in cultures of human T cells stimulated with Candida albicans antigen. Proliferation of T cells from six type 1 diabetic and six non-diabetic control subjects was significantly inhibited (both P <0.05) in glucose-free medium, and at a glucose concentration of 80 mmol 1⁻¹ as compared with cultures containing glucose at physiological concentration (5 mmol 1⁻¹). 16 and 32 mmol 1⁻¹ 3-HB also inhibited T cell proliferation in the presence of 5 mmol 1⁻¹ glucose ( P <0.05). The effect of glucose and 3-HB were not additive and the inhibition was not due to cell death. 32 mmol 1⁻¹ 3-HB had less effect when present solely during antigen pulsing than during subsequent lymphocyte stimulation, and was effective even when added after 72 h of a six day culture. This suggests that ketosis affects T cell proliferation more than antigen processing and presentation. We conclude that human antigen-specific T cell proliferation is inhibited in vitro only by concentrations of 3-HB encountered in moderately severe diabetic ketoacidosis, and by glucose concentrations found in severe hyperosmolar non-ketotic coma. The impairment of T cell function under such extreme conditions could be implicated in the close association of diabetic ketoacidosis with deep fungal infections, particularly invasive mucormycosis.     

Plasma amino acid levels in hyperosmolar nonketotic diabetic coma

The plasma amino acid levels in five patients with hyperosmolar nonketotic diabetic coma and in seven normal subjects were analysed. In the patients with hyperosmolar nonketotic diabetic coma, total amino acids were generally low, especially, the concentrations and the molar ratios of arginine, taurine and serine were significantly low, and ornithine decreased only at the concentration. The level of phenylalanine increased both at the concentration and the molar ratio, and tyrosine did only at the molar ratio. The significance of such changes in the plasma is discussed in relation to diabetic ketoacidosis or lactic acidosis.     

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.     

Ketonaemia in Uncontrolled Diabetes Mellitus

Blood ketone bodies, serum insulin levels, and plasma free fatty acids were examined in a series of patients with “non-ketotic diabetic coma” and compared with the findings in ketoacidotic subjects. Serum insulin levels in six “non ketotic” patients ranged between 1 and 25 μu./ml. and were not significantly different from levels reported in patients with ketoacidosis. In addition, plasma free fatty acids were shown to be unrelated to the degree of ketonaemia. The investigation shows that neither the levels of serum insulin nor those of free fatty acids can explain the absence of hyperketonaemia in some cases.     

Plasma 11-Hydroxycorticosteroid and Growth Hormone Levels in Acute Medical Illnesses

Adrenal cortical response in acute medical illness has been studied by measuring the plasma 11-hydroxycorticosteroid (11-OHCS) concentration in 178 patients. Those with unbalanced diabetes, acute infections, and severe myocardial infarction had high levels. The results obtained suggest that in a patient with a severe infection and hypotension a plasma 11-OHCS level of less than 15 μg./100 ml. indicates an inadequate adrenal cortical response, and one patient with septicaemia and temporary adrenal cortical insufficiency is described. Growth hormone levels were increased in patients with severe diabetic ketosis but not in those with hyperosmolar non-ketotic diabetic coma.     

Effects of ketoacidosis and puberty on basal and TRH-stimulated thyroid hormones and TSH in children with diabetes mellitus

Basal and TRH-stimulated thyroid hormones and TSH were evaluated in two groups of prepubertal and pubertal diabetics: group B - 45 children without ketoacidosis; group C - 16 children with ketoacidosis. The diabetic patients showed no signs of diabetic microangiopathy. Fifty-three healthy subjects served as controls (group A). T4, T3, FT4 and FT3 serum levels were reduced in diabetics, particularly in ketotic ones; T4 and T3 values were lower in pubertal than in prepubertal non-ketotic diabetics and in pubertal than in prepubertal controls, while no significant difference was observed between pubertal and prepubertal ketotic patients. Moreover, no difference in rT3 serum concentrations was found between group A, B and C, but non-ketotic and ketotic pubertals showed a significant rT3 reduction if compared with non-ketotic and ketotic prepubertals and with healthy pubertals. TBG was lower in group B and group C diabetics than in controls. After TRH stimulus, T3 levels showed a significant increase both in controls and in non-ketotic diabetics, while no variation was observed in ketotic children; furthermore, at 120 minutes T3 values were lower in diabetic than in healthy children, particularly in ketotic ones. Basal TSH serum concentrations were reduced in ketotic diabetics, while no difference was found between nonketotic and control subjects. After TRH stimulus, TSH peak was higher in pubertal non-ketotic diabetics than in pubertal controls, while no difference was found between prepubertal and pubertal diabetics, both in non-ketotic and in ketotic status.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of 3-hydroxybutyrate and hyperosmolarity on glucagon release from isolated perfused canine pancreas

The effects of 3-hydroxybutyrate (3-OHB) and hyperosmolarity on glucagon secretion were examined in the isolated perfused canine pancreas. When 3-OHB was infused for 15 min into the pancreas perfused with 2.8 mM glucose, 5 and 20 mM sodium 3-OHB inhibited it after a transient stimulation, whereas a similar transient stimulation was observed also by the infusion of 20 mM NaCl in a control experiment. The above inhibition was not observed under the perfusate condition of 5.5 mM glucose plus 10 mM arginine. When the isolated canine pancreas was perfused under the perfusate condition of acidosis (pH 7.1), ketoacidosis (pH 7.1 and 20 mM 3-OHB) or hyperosmolarity (+60 mOsm/kg with sucrose) throughout the experiment, the glucagon concentrations produced by 2.8 mM glucose under the ketoacidotic and hyperosmolar conditions, were less than half of those obtained under the standard condition. The insulin level was not influenced by the above perfusate conditions. These results suggest that 3-OHB inhibits glucagon secretion stimulated by glucopenia, but does not inhibit it stimulated by amino acids, and that hyperosmolarity inhibits glucagon secretion but does not inhibit insulin secretion. The pathophysiological significance of these results must be slight, considering the presence of hyperglucagonemia during prolonged starvation or diabetic ketoacidosis.     

Non-ketotic hyperosmolar coma with insulin resistance in a 12-year-old girl

Although the frequency of recognition of the syndrome of non-ketotic hyperosmolar coma is increasing in all age groups the mortality rate remains high. This paper reports the occurrence of this syndrome in a 12-year-old girl. The pathogenesis is discussed and a planned approach to the management of circulatory collapse, hypokalemia, hyperglycemia and hyperosmolarity over the initial 24 hours is proposed. The phenomenon of insulin resistance which was observed in this case is a rare complication of this syndrome. Awareness of the occurrence of this syndrome in all age groups, early recognition of its features and a planned approach to management are mandatory to reduce the very high mortality rate.     

Plasma insulin and glucagon and their release from pancreatic islet in hyperosmolar diabetic rat.

In order to investigate the metabolic abnormalities in hyperosmolar diabetes from the viewpoint of insulin or glucagon, experimental hyperosmolar diabetes was produced by a combination of cortisol injection and water deprivation or only by the latter in streptozotocin-induced moderately hyperglycemic rat. They had a high blood glucose level and high plasma osmotic pressure. Fasting plasma insulin tended to decrease in the dehydrated state whether diabetic or not. Fasting plasma glucagon was increased to 0.047 +/- 0.009 nmol/l (P less than 0.05) in the non-diabetic dehydrated state (normal 0.026 +/- 0.004 nmol/l), and a similar high level of plasma glucagon was observed in the dehydrated diabetic rat (0.052 +/- 0.020 nmol/l), especially after cortisol treatment. In isolated rat islet, insulin released from the dehydrated diabetic rat at a high concentration of glucose was to some extent lower than that of diabetic rat, and released IRG vice versa. The insulin:glucagon ratio in the presence of high glucose was significantly lower in the dehydrated diabetic rat than in the normal rat (P less than 0.01). In the diabetic rat this ratio was not significantly different. This finding was also consistent with the results of in vivo experiments. Thus more catabolic hormonal changes were found in in vivo and in vitro studies in the hyperosmolar diabetic rat.     

West Indian diabetic population of a large inner city diabetic clinic.

West Indians form a sizable minority of diabetics attending many inner city diabetic clinics. There are 554 diabetics of West Indian origin on our computer files--7% of the total recorded clinic population. Of these 554 patients (56% female, 44% male), 70% have been diagnosed within the past five years; and only 9% have had diabetes for over 10 years; in only five (1%) was diabetes diagnosed before the age of 20. Sixteen per cent were taking insulin, but only 4% of the total West Indian population were truly insulin dependent. Of 65 patients admitted in hyperglycaemic coma or precoma over the past three years, 10 were of West Indian origin; eight of these 10 had hyperosmolar coma compared with only six of the remaining 55. We conclude that diabetics of West Indian origin attending our clinic show differences in the distribution of age and duration of diabetes from the caucasian population. Most are non-insulin dependent, and the frequency of hyperosmolar coma is higher than that of ketoacidosis. Diabetics of West Indian origin may have a different pattern of disease from the rest of the clinic population.     

Treatment of Diabetic Coma with Continuous Low-dose Infusion of Insulin

Thirty-eight patients in diabetic coma from four different centres were treated with a continuous low-dose intravenous infusion of insulin at an average dose of 7·2 IU/hr. All patients recovered rapidly except for one profoundly shocked patient who died. The mean fall in plasma glucose was 58% four hours after the start of insulin. Blood ketone bodies and plasma free fatty acids showed a similar response. There was no significant difference in plasma glucose response according to severity of acidosis or previous treatment with insulin. Hypokalaemia was uncommon. In the treatment of diabetic coma this technique has proved simple, safe, and effective.     

糖尿病急性并发症合并横纹肌溶解患者临床特征及预后

目的:分析糖尿病急性并发症患者合并横纹肌溶解的临床特征及预后,为临床及时诊断和治疗提供依据。方法:对我院2003年1月～2009年5月住院患者查阅病例资料,糖尿病酮症酸中毒及高血糖高渗状态患者根据肌酸激酶升高与否,分为血清肌酸激酶升高组(A组)和血清肌酸激酶正常组(B组),比较两组临床特征及预后。结果:A、B两组比较,A组较B组血清尿素氮、肌酐、肌红蛋白明显升高,住院时间明显延长,但出院时A组较B组每天每公斤胰岛素剂量减少,差异有统计学意义(P<0.05)。A组中3例患者血清肌酸激酶大于1000U/L,符合横纹肌溶解综合征诊断标准。结论:糖尿病酮酸中毒及高血糖高渗状态患者应重视肌酶检查,早期诊断横纹肌溶解综合征,保护肾脏和胰岛β细胞功能,缩短住院时间。     

<Emphasis Type="Italic">Rhizopus arrhizus</Emphasis> Invasive Infection due to Self-Inflicted Scratch Injuries in a Diabetic Patient with Non-ketotic Acidosis

Mucormycosis is a rare infection caused by members included in the subphylum Mucoromycotina. Characterized by the histopathological hallmark of angioinvasion, these infections affect most often patients with certain underlying conditions carrying immunosuppression (haematological neoplasias, diabetic ketoacidosis and other forms of acidosis, and iron overload) or immunocompetent patients with traumatic mucocutaneous barriers breakdown and direct inoculation of the mould. A case is presented in which a rare underlying condition (non-ketotic acidosis) and a rare cause of cutaneous injuries collide. Prognosis, treatment options and management decisions are described thoroughly.