Correction Of Diabetic Ketoacidosis Research Articles

Inflammatory cytokine and plasma C-reactive protein response to ketoacidosis in adults with type 1 diabetes: Egyptian multicenter study

BackgroundIn adults with diabetic ketoacidosis (DKA), high plasma levels of C-reactive protein (CRP) and inflammatory cytokines such as interleukin-6 (IL-6) were reported to be sensitive markers of infection. However, elevation of both CRP and the pro-inflammatory cytokines which regulate CRP are probable without infection and may act as indicator of systemic inflammatory response (SIR). So, we wanted to determine if increased plasma CRP levels occur in young patients with severe DKA who do not have clinical evidence of infection and to relate observed changes in CRP level to the pro-inflammatory cytokine levels.ResultsUpon admission of 30 DKA patients with age ranging from 17 to 40 years, we found significant elevation of CRP (P = 0.001) and IL-6 (P = 0.001) in DKA patients than control group. After resolution of DKA, there was significant reduction in CRP and IL-6 compared to before DKA correction (P value = 0.054 and 0.001), respectively. There was a significant negative correlation between CRP after correction of DKA and RBCs (P = 0.042), and serum K (P = 0.021) and between CRP prior to DKA correction and PH (P = 0.025).ConclusionsPatients with DKA without infection had increased levels of CRP and inflammatory cytokines. Intensive insulin therapy has a powerful anti-inflammatory effect that, at the time of DKA improvement, can normalize levels of CRP and inflammatory cytokines, and this beneficial effect is greater for IL-6 than CRP.

The Utility of Continuous Subcutaneous Insulin Infusion for Management of Mild to Moderate Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is the commonest hyperglycemic emergency in people with diabetes. Fluid and insulin, commonly via intravenous route, is the mainstay of treatment; however, other methods of insulin administration have been tried. In this study, we aimed at comparing the efficacy and safety of continuous subcutaneous insulin infusion (CSII) to intravenous (IV) insulin infusion protocol using a short acting insulin analogue, glulisine, in patients with mild to moderate DKA. This is a prospective randomized controlled trial including 30 patients with DKA randomly assigned to receive Glulisine insulin via CSII or IV infusion. Metabolic parameters were observed till resolution of DKA. Primary end point was assessment of the duration till resolution. Secondary end points included total length of hospitalization, amount of insulin used and the number of hypoglycemic events. There were no statistical differences in the mean duration of treatment until correction of DKA being 16.58 ± 3.68 hours for CSII group versus 14.60 ± 3.2 hours in the IV group, p=0.136. There was no mortality and no differences in the length of hospital stay, or the number of hypoglycemic events among treatment groups. However, the total amount of insulin administration until resolution of ketoacidosis was significantly higher, 61.50 ± 13.89 units, in CSII group compared to 46.60 ± 13.53 units in the IV group, p=0.009. We concluded that the use of CSII of glulisine insulin represented a safe and effective alternative to the use of IV glulisine in the management of patients with mild to moderate DKA.

Acute Bilateral Cataract in Type 1 Diabetes Mellitus.

We report a case of a 17-year old boy, who presented acute bilateral cataract and complete vision loss within six days, three months after the diagnosis of Type 1 Diabetes Mellitus (T1DM) under optimal metabolic control (HbA1c 6%). At presentation (HbA1c 10.4%) and after correction of diabetic ketoacidosis (pH 6.917) and the beginning of intensified insulin treatment with insulin glargine once daily and insulin aspart before meals,the patient underwent full ophthalmologic examination,which was completely normal. Only few cases with acute bilateral cataract - all relatively shortly after the diagnosis of T1DM - have been reported. Several hypotheses have been drawn but the exact mechanism of this phenomenon remains unclear. The interesting finding in our case was the clearly elevated insulin autoantibodies (IAA) at the time of cataract formation, negative however at presentation. The relation between the elevation of IAA and cataract formation should be further investigated in diabetic patients.

Increased systemic Th17 cytokines are associated with diastolic dysfunction in children and adolescents with diabetic ketoacidosis.

Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in children with T1DM, but its pathogenesis is not well understood. We studied the relationships of systemic inflammatory cytokines/chemokines and cardiac function in 17 children with T1DM during and after correction of diabetic ketoacidosis (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6–12 hours into treatment of DKA compared to values after DKA resolution. Eight patients displayed at least one parameter of diastolic abnormality (DA) during acute DKA. Significant associations were present between nine of the cytokine/chemokine levels and the DA over time. Interestingly, four of these nine interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17 mediated cell response. Both the DA and CCL7 and IL-12p40, had independent associations with African American patients. Thus, we report occurrence of a systemic inflammatory response and the presence of cardiac diastolic dysfunction in a subset of young T1DM patients during acute DKA.

Eating disorders and diabetic ketoacidosis in a pregnant woman with type 1 diabetes: A case report

To describe a case of diabetic ketoacidosis (DKA) in a pregnant woman with type 1 diabetes (T1DM) and disordered eating behaviour treated with a continuous subcutaneous insulin infusion, and to discuss some aspects of the monitoring and management of DKA in pregnancy and whether a pump is the safest therapeutic choice in the presence of some eating disorders. This 26-year-old Caucasian woman affected by T1DM was hospitalised during the last weeks of her fourth pregnancy because of DKA due to disordered eating. She was treated with a fluid infusion, intravenous insulin, and her electrolyte imbalance was carefully corrected. An elective cesarean section was performed after the correction of DKA in the 34th week (+6 days) of gestation. We suggest that pregnancy in T1DM women with eating disorders may not be rare. The prevention, early recognition and aggressive management of DKA can minimise the possible complications, and is mandatory for the safety of the fetus and mother.

An 18-yr prospective study of pediatric diabetic ketoacidosis: an approach to minimizing the risk of brain herniation during treatment

During the late 1900s, raised intracranial pressure (ICP) during treatment of pediatric diabetic ketoacidosis (DKA) surfaced as the most important cause of morbidity and mortality in pediatric DKA. The contribution of fluid and electrolyte therapy to neurologic deterioration during treatment remains controversial. We proposed a physiologic approach to treatment of DKA, incorporating the principles of rehydration of hypertonic states. Consecutive episodes of pediatric DKA were managed using continuous intravenous insulin, an individualized assessment of the degree of dehydration, and rehydration solutions of tonicity approximating that of the patient. Gradual replacement of the volume of deficit after correction of shock, if present, was planned over 48 h with special attention to changes in effective osmolality along with intensive cardiorespiratory, neurologic, and biochemical monitoring. Mannitol was given for signs or symptoms of raised ICP. Six hundred and thirty-five consecutive episodes of pediatric DKA were treated from January 1988 to September 2005. Means +/- standard deviation (SD) for initial measured concentrations of total carbon dioxide, glucose, and urea nitrogen were 7.8 +/- 3.3 mmol/L, 602 +/- 271 mg/dL (33.4 +/- 15 mmol/L), and 21 +/- 1 mg/dL (7.4 +/- 3.6 mmol/L), respectively. Pretreatment blood gases were available for 477 episodes. The mean initial partial pressures of arterial and venous carbon dioxide +/- SD were 16.8 +/- 7 mmHg (kP(a)CO(2)= 2.24 +/- 0.93) for n = 308 and 26.6 +/- 7 mmHg (kP(v)CO(2)= 3.54 +/- 0.93) for n = 169, respectively. Although repair was planned to occur over 48 h, the mean time to achieve clinical rehydration and correction of DKA was 11.6 +/- 6.2 h. Mannitol was given in 35 (5.5%) episodes. There was no neurologic morbidity or mortality. Management of pediatric DKA using this multifaceted physiologic approach and the principles of rehydration described is safe and appears to minimize the risk of brain herniation during treatment.

Retinal vascular integrity following correction of diabetic ketoacidosis in children and adolescents

Objective Increased permeability of the cerebral microvasculature occurs during the treatment of diabetic ketoacidosis (DKA). Microvascular changes consistent with diabetic retinopathy have been reported prior to and after the treatment of DKA. This study evaluated the structural and functional aspects of the retina immediately following the correction of DKA. Methods Seven young patients had comprehensive ophthalmologic examinations, including fluorescein angiography, within 24 h after the correction of severe DKA (pH <7.2). Results None of the patients had clinical, photographic, or angiographic evidence of a retinal abnormality. Conclusion The blood–retinal barrier (BRB) does not experience the same degree of perturbation as the blood–brain barrier (BBB) does and may be a protected site during the insult of DKA and its treatment. The greater stability of the retinal microvasculature may be due to the increased number of pericytes in the BRB in comparison with the BBB.

Complement activation in diabetic ketoacidosis and its treatment

Recent studies support the presence of an inflammatory response during the treatment of diabetic ketoacidosis (DKA). The objectives of this study were to monitor the complement activation products C3a, C4a, Bb, and C5b-9 prior to, during, and after correction of DKA. All patients had increased levels of C3a at 6–8 h and 24 h ( P < 0.05). C4a was increased in only one patient. Bb showed an upward trend at 6–8 h, and was significantly elevated at 24 h ( P < 0.05); sC5b-9 was elevated in all patients prior to treatment or in the first 6–8 h of treatment. Results indicate that the alternative pathway may be the primary pathway of activation. These results extend the observation that both DKA and its treatment produce varying degrees of immunologic stress during the time when acute complications are most likely to occur.

Serum Potassium and Acid-base Parameters in Severe Dialysis-associated Hyperglycemia Treated with Insulin Therapy

We analyzed the changes in serum potassium concentration ([K]) and acid-base parameters in 43 episodes of dialysis-associated hyperglycemia (serum glucose level > 33.3 mmol/L), 22 of which were characterized as diabetic ketoacidosis (DKA) and the remaining 21 as nonketotic hyperglycemia (NKH). All episodes were treated with insulin therapy only. Age, gender, initial and final serum values of glucose, sodium, chloride, tonicity and osmolality did not differ between DKA and NKH. At presentation, serum values of [K] (DKA 6.2 +/- 1.3 mmol/L; NKH 5.2 +/- 1.5 mmol/L) and anion gap [AG] (DKA 27.2 +/- 6.4 mEq/L; NKH 15.4 +/- 3.5 mEq/L) were higher in DKA, whereas serum total carbon dioxide content [TCO2 ] (DKA 12.0 +/- 4.6 mmol/L; NKH 22.5 +/- 3.1 mmol/L), arterial blood pH (DKA 7.15 +/- 0.09; NKH 7.43 +/- 0.07) and arterial blood PaCO2 (DKA 26.2 +/- 12.3 mm Hg; NKH 34.5 +/- 6.7 mm Hg) were higher in NKH. At the end of insulin treatment, serum values of [K] (DKA 4.0 +/- 0.7 mmol/L, NKH 4.0 +/- 0.5 mmol/L), [AG] (DKA 16.3 +/- 5.4 mEq/L, NKH 14.9 +/- 3.0 mEq/L), [TCO2 ] (DKA 23.5 +/- 5.0 mmol/L, NKH 24.1 +/- 4.2 mmol/L), arterial blood pH (DKA 7.42 +/- 0.09, NKH 7.51 +/- 0.14) and arterial blood PaCO2 (DKA 31.8 +/- 6.7 mm Hg, NKH 34.2 +/- 8.3 mm Hg) did not differ between the two groups. Linear regression of the decrease in serum [K] value during treatment, (Delta[K]), on the presenting serum [K] concentration,([K]2 ), was: DKA, Delta[K] = 2.78 - 0.81 x [K]2 , r = -0.85, p < 0.001; NKH, Delta[K] = 2.44 - 0.71 x [K]2 , r = -0.90, p < 0.001. The slopes of the regressions were not significantly different. Stepwise logistic regression including both DKA and NKH cases identified the presenting serum [K] level and the change in serum [TCO2 ] value during treatment as the predictors of Delta[K] (R2 = 0.81). Hyperkalemia is a feature of severe hyperglycemia (DKA or NKH) occurring in patients on dialysis. Insulin administration brings about correction of DKA and return of serum [K] concentration to the normal range in the majority of the hyperglycemic episodes without the need for other measures. The initial serum [K] value and the change in serum [TCO2 ] level during treatment influence the decrease in serum [K] value during treatment of dialysis-associated hyperglycemia with insulin.

Study of Subclinical Cerebral Edema in Diabetic Ketoacidosis by Magnetic Resonance Imaging T2 Relaxometry and Apparent Diffusion Coefficient Maps

Cerebral edema is the most significant complication in children with diabetic ketoacidosis (DKA). Our goal was to study whether subclinical cerebral edema was preferentially vasogenic or cytotoxic. Magnetic resonance imaging (MRI)—diffusion-weighted imaging (DWI) and T2 relaxometry (T2R)—were obtained in pediatric patients presenting with severe diabetic ketoacidosis (DKA) 6–12 hours after initial DKA treatment and stabilization and 96 hours after correction of DKA. T2 relaxometry was significantly increased during treatment in both white and gray matter, in comparison to the absolute T2R values 96 hours after correction of DKA (p = .034). Classic intracellular cytotoxic edema could not be detected, based on the lack of a statistically significant decrease in ADC values. ADC values were instead elevated, implying a large component of cell membrane water diffusion, correlating with the elevated white and gray matter T2R. We discuss the findings in relation to cerebral blood volume, cerebral vasoregulatory dysfunction, and cerebral hyperemia.

Early Identification of Rhinocerebral Mucormycosis

Mucormycosis is an acute and often fatal infection caused by a fungus of the Mucorales order of the Zygomycetes class. In the majority of cases, it is associated with an underlying disorder, such as diabetes mellitus with ketoacidosis, or with immunocompromising factors, but it may appear in healthy people, although rarely. Early diagnosis and treatment are critical to prevent an otherwise fatal outcome. This article presents and discusses the early (alarming) signs and symptoms and the predisposing factors that should be considered to avoid delays in diagnosis. We review seven cases of rhinocerebral mucormycosis admitted to our hospitals from 1998 to 2003. All patients had an underlying immunocompromising factor and/or diabetes mellitus. Five patients had palatal necrotic ulcers and/or black eschars. Three patients had unilateral blindness, and two patients required orbital exenteration. Four patients died because of a delayed diagnosis. Early diagnosis is critical in the prevention of intracranial extension of the infection, which is the cause of death in 80% of cases. Therefore, a high index of clinical suspicion is essential in immunocompromised or diabetic patients with acute sinus infection. Identification of a fungal organism on histopathology is the most specific element for diagnosis. A team approach to management is recommended for early surgical debridement, correction of diabetic ketoacidosis, and systemic antifungal agents. Timely medical-surgical treatment proves extremely important for prognosis.

Lipid peroxidation and antioxidant vitamins prior to, during, and after correction of diabetic ketoacidosis

Oxidative stress plays an important role in the chronic complications of insulin-dependent diabetes mellitus (IDDM). Hyperketonemia, as well as hyperglycemia, is involved in the generation of oxygen-free radicals. We have studied the degree of oxidative stress in six patients before, during, and after correction of diabetic ketoacidosis (DKA) by determining the plasma ratios of C20 and C18 fatty acids to C16 fatty acids in the cholesteryl esters of the lipoproteins as well as in the plasma concentrations of the antioxidant vitamins A, C, and E. Lipid peroxidation was slightly increased prior to treatment. However, the C20/C16 ratio at 120 h was significantly decreased in comparison to the ratio at pretreatment (P<.025), at 6–8 h (P<.005), and at 24 h (P<.025). The C18/16 ratio at 120 h was also decreased in comparison to the ratio at 6–8 h (P<.025), indicating an increase in lipid peroxidation after correction of DKA. Vitamin A was below normal at pretreatment and was increased at 120 h (P<.05). Vitamin C was normal at pretreatment and decreased to low normal at 24 h (P<.005). Vitamin E was normal at pretreatment and decreased to below normal at 24 and 120 h, although the changes were not statistically significant. These data demonstrate that there is an increase in lipid peroxidation after the correction of DKA and therefore support the position that administering antioxidant vitamins during the treatment of DKA could be beneficial in minimizing oxidative stress and possibly both the acute and chronic complications of IDDM.

Management of Limited Rhino-orbital Mucormycosis without Exenteration

Eight cases of rhino-orbital mucormycosis managed successfully without exenteration were reviewed. The favorable outcome was attributable to early diagnosis and management of focal areas of fungus infection. Treatment included: (1) correction of diabetic ketoacidosis or other concomitant metabolic derangement; (2) wide local excision and debridement of all involved and devitalized oral, nasal, sinus, and orbital tissue, while establishing adequate sinus and orbital drainage; (3) daily irrigation and packing of the involved orbital and paranasal areas with amphotericin B; and (4) intravenous amphotericin B. This represents the largest reported series of rhino-orbital mucormycosis survivors without mutilating surgery and with unaltered visual acuity.