Heterogeneity in presentation of hyperglycaemia during COVID-19 pandemic: A proposed classification.

Diabetes and hyperglycemia occurring during COVID-19 era have implications for COVID-19 related morbidity/mortality. In this brief review, we have attempted to categorise and classify such heterogenous hyperglycemic states. During COVID-19 pandemic broadly two types of hyperglycemia were seen: one in patients without COVID-19 infection and second in patients with COVID-19 infection. Patients not inflicted with COVID-19 infection and diagnosed with either type 2 diabetes mellitus (T2DM) or type 1 diabetes mellitus (T1DM) show more severe hyperglycemia and more ketoacidosis, respectively. In former, it could be attributed to weight gain, decreased exercise, stress and in both type of diabetes, due to delayed diagnosis during lockdown and pandemic. In patients with COVID-19 and associated pneumonia, altered glucose metabolism leading to hyperglycemia could be due to corticosteroids, cytokine storm, damage to pancreatic beta cells, or combination of these factors. Some of these patients present with diabetic ketoacidosis, hyperglycemic hyperosmolar state or both. We have provided a framework for categorisation of hyperglycemic states, which could be consolidated/revised in future based on new research data.

Evaluation and management of ketosis-prone diabetes.

INTRODUCTION: Patients presenting with diabetic ketoacidosis (DKA) who lack the classic phenotype of autoimmune type 1 diabetes have become increasingly identified in recent decades. This has led to the recognition of heterogeneous syndromes of 'ketosis-prone diabetes' (KPD). Evaluation and optimal management of KPD differs from that of 'typical' type 1 or type 2 diabetes. Awareness of these differences and a systematic approach to diagnosis and treatment can improve glycemic control and prevent both acute and chronic complications of diabetes. AREAS COVERED: This article reviews the Aß classification scheme ('A' for autoantibody status and 'ß' for beta cell functional reserve) which accurately delineates subgroups of KPD, and addresses the relevance of defining these subgroups for clinical outcomes and long-term insulin dependence. Subsequently, the detailed evaluation and management of KPD patients after their index DKA episode is described. EXPERT COMMENTARY: Among patients presenting with DKA, it is important to diagnose specific subgroups of KPD and not assume that they represent exclusively patients with autoimmune type 1 diabetes. The Aß classification is an accurate aid to diagnosis, and permits optimal management of the subgroups (e.g., insulin treatment for the ß- subgroups; follow-up testing and a range of treatment options for the ß+ subgroups).

Autoantibodies to the IA-2 Extracellular Domain Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes.

OBJECTIVE: Autoantibodies directed against tyrosine phosphatase IA-2 antibody (IA-2 Ab) are diagnostic for autoimmune type 1 diabetes. Conventional assays target the intracellular domain of IA-2. Among patients with ketosis-prone diabetes (KPD), characterized by presentation with diabetic ketoacidosis (DKA), >60% of adults lack three classic islet autoantibodies-IA-2, GAD65, and ZnT8 Abs-associated with type 1 diabetes. We aimed to determine whether apparently autoantibody-negative ("A-") KPD patients possess occult IA-2 Ab directed against full-length IA-2 (IA-2FL) or its extracellular domain (IA-2EC). RESEARCH DESIGN AND METHODS: We developed an assay that targets IA-2FL and IA-2EC and used it to analyze 288 subjects with A- KPD. RESULTS: Ten A- KPD patients were positive for IA-2EC Ab (3.5%), and three were also positive for IA-2FL Ab (1.0%), similar to frequencies in type 1 and type 2 diabetes. CONCLUSIONS: Measurement of IA-2FL Ab and IA-2EC Ab improves the accuracy of the Aß classification of KPD patients.

New approaches to the use of insulin in patients with diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is one of the most common and serious acute complications of diabetes and is a significant cause of morbidity and mortality. In the last decade the mortality rate from DKA has declined because of greater recognition and improvements in its management. The current available guidelines state that the most effective means of insulin delivery during DKA is a continuous infusion of regular insulin, usually referred to as continuous low-dose insulin infusion. However, the cost of this treatment is usually quite high, because patients are required to be admitted to an intensive care unit in order to be monitored closely. New analogs of human insulin that have a rapid onset of action have become available in the past decade and represent potential alternatives to the use of regular insulin in the treatment of DKA. In several trials it has been demonstrated that the use of subcutaneous rapid-acting insulin analogs represents a safe, cost-effective and technically simpler treatment that precludes intensive care unit admission without significant differences in outcome in the management of patients with mild to moderate, uncomplicated DKA. The long-acting insulin analog may have a role in facilitating the transition from continuous intravenous insulin infusion to subcutaneous maintenance therapy in patients with DKA. This avoids rebound hyperglycaemia and ketogenesis when intravenous insulin is stopped and may avoid excess length of stay.

[The classification and prognostic implication of islet ß cell function before and in remission period in newly diagnosed diabetic patients with ketosis].

OBJECTIVE: To observe ß cell function in newly diagnosed diabetic patients with ketosis before and in remission period and evaluate its classification and predictive value. METHODS: A total of 206 patients newly diagnosed as diabetic ketosis who had been treated with intensive insulin therapy in our hospital and entered in the "honeymoon" after the withdraw of insulin therapy were followed for 36 months from onset of diabetes. They were divided into two groups of type 1 and type 2 diabetes (group A and B), according to the dependence or independence on insulin treatment. The ß cell function of the two groups before and in remission period was compared by oral glucose tolerance test (OGTT). ß cell function was measured with the AUC of insulin and C-peptide and homeostatic model assessment ß-cell function (HOMA-ß), while homeostatic model assessment insulin resistant (HOMA-IR) for insulin resistant. The duration of the "honeymoon" and the change of insulin and C-peptide curve before and in "honeymoon" were also observed. RESULTS: The AUC of insulin and C-peptide, the HOMA-ß and the HOMA-IR before and after the intensive insulin treatment were lower in group A than that in group B [before the insulin treatment: (10.18 ± 2.36) mIU×h×L(-1) vs (20.28 ± 6.89) mIU×h×L(-1), (1.56 ± 0.53) µg×h×L(-1) vs (3.75 ± 0.67) µg×h×L(-1), 3.68 ± 1.08 vs 18.20 ± 6.59, 1.22 ± 0.49 vs 3.06 ± 1.54, respectively; after the insulin treatment: (29.86 ± 8.65) mIU×h×L(-1) vs (93.35 ± 19.42) mIU×h×L(-1), (3.99 ± 0.79) µg×h×L(-1) vs (12.54 ± 3.83) µg×h×L(-1), 8.50 ± 2.46 vs 56.17 ± 19.42, 0.63 ± 0.56 vs 1.42 ± 0.78, respectively]. The duration of the "honeymoon" in group A was significantly shorter than in group B [(7.9 ± 5.2) months vs (20.9 ± 9.9) months]. In oral glucose insulin and C-peptide release test, the peak of insulin and C-peptide releasing curve in group A was brought forward by a half to 1 hour after intensive treatment while delayed in group B by 1 or 2 hours. The releasing peak of insulin and C-peptide in group A was less than two folds of the basic value, while four to ten fold of the basic value in group B. The positive ratio of glutamic acid decarboxylase antibody, insulin autoantibody and insular cellular antibody in group A and group B were 21.2% vs 4.8%, 18.1% vs 3.3%, 9.2% vs 10.6%, respectively. CONCLUSIONS: Of all the patients newly diagnosed as diabetes ketosis who had entered into the honeymoon after intensive insulin therapy, 91% were type 2 diabetes. Inferior ß cell function before insulin therapy, weaker remission after insulin therapy and shorter duration of remission period suggest the classification of type 1 diabetes.

Clinical profile and outcomes of paediatric patients with diabetic ketoacidosis at a tertiary care hospital in Pakistan.

OBJECTIVES: This study aims to present an experience in the management and clinical features of 88 children presenting with diabetic ketoacidosis (DKA) from Pakistan. METHODS: A retrospective medical chart review of all patients, < or = 15 years of age, who presented to the Aga Khan University Hospital, Karachi, Pakistan in the last ten years with a diagnosis of diabetic ketoacidosis was carried out. Severity of DKA was defined as mild (venous pH < 7.30 or bicarbonate=15mEq/l), moderate (venous pH < 7.2 or bicarbonate = 10 mEq/l) and severe (venous pH < 7 or bicarbonate < 5 mEq/l). These classes correspond to 1st, 2nd and 3rd degrees of diabetic ketoacidosis severity respectively. Cases in which diabetic ketoacidosis had occurred at onset of diabetic diagnosis were not included in the study. RESULTS: Mean age was 7.5 +/- 3.6 years; 58 (66%) patients were male. Twenty six patients had mild diabetic ketoacidosis, 44 had moderate while 18 had severe diabetic ketoacidosis at the time of presentation. Severity of diabetic ketoacidosis was significantly associated with the presence of infection, history of omission of insulin, poor compliance, presence of shock at time of presentation, length of stay in the hospital, final outcome (p < 0.01 for each of these associations) and Glasgow Coma Scale score (p = 0.02). Mortality in this series was 3.4%. CONCLUSION: Poor compliance was associated with the severity of diabetic ketoacidosis. Paediatric endocrinologists' should ensure that patients and their parents understand the importance of the need for regular insulin injections and regular monitoring of blood glucose.

Clinical characteristics of Korean patients with new-onset diabetes presenting with diabetic ketoacidosis.

We studied 65 adult patients without a history of diabetes who were diagnosed with diabetic ketoacidosis. Ketosis-prone type 2 diabetes was common (42%) among this group of Korean patients with new-onset diabetes presenting with diabetic ketoacidosis. These patients were younger, showed a greater defect in insulin secretion.

Diabetes classification: grey zones, sound and smoke: Action LADA 1.

Diseases gain identity from clinical phenotype as well as genetic and environmental aetiology. The definition of type 1 diabetes is clinically exclusive, comprising patients who are considered insulin dependent at diagnosis, whilst the definition of type 2 diabetes is inclusive, only excluding those who are initially insulin dependent. Ketosis-prone diabetes (KPD) and latent autoimmune diabetes in adults (LADA) are each exclusive forms of diabetes which are, at least initially, clinically distinct from type 2 diabetes and type 1 diabetes, and each have a different natural history from these major types of diabetes.KPD can be diagnosed unequivocally as diabetes presenting with the categorical clinical feature, ketoacidosis. In contrast, LADA can be diagnosed by the co-occurrence of three traits, not one of which is categorical or exclusive to the condition: adult-onset non-insulin-requiring diabetes, an islet autoantibody such as glutamic acid decarboxylase autoantibodies (GADA) or cytoplasmic islet cell autoantibodies (ICA), and no need for insulin treatment for several months post-diagnosis. But while some would split diabetes into distinct subtypes, there is a strong case that these subtypes form a continuum of varying severity of immune and metabolic dysfunction modified by genetic and non-genetic factors. This article discusses the nature of disease classification in general, and KPD and LADA in particular, emphasizing the potential value and pitfalls in classifying diabetes and suggesting a need for more research in this area.

Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration.

OBJECTIVE: To ascertain whether initial depression of conscious level in children with diabetic ketoacidosis (DKA) is related to hyperosmolality, acidosis or other factors. METHODS: In 225 episodes of DKA without evidence of cerebral edema, we examined the relationship between conscious level and initial biochemical variables. We contrasted these findings with those in 42 children who later developed cerebral oedema. RESULTS: On admission, 42/225 (19%) had mild (pH 7.26-7.35); 96 (44%) moderate (pH 7.11-7.25); and 80 (37%) severe DKA (pH

Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes.

Ketosis-prone diabetes is heterogeneous. Its causes could include novel beta-cell functional defects. To characterize such defects, 103 patients with diabetic ketoacidosis were evaluated for beta-cell autoimmunity and human leukocyte antigen (HLA) class II alleles, with longitudinal measurements of beta-cell function and biochemical and clinical parameters. They were classified into four A beta groups, based on the presence of glutamic acid decarboxylase (GAD)65, GAD67, or IA-2 autoantibodies (A+ or A-) and beta-cell functional reserve (beta+ or beta-). The group distribution was: 18 A+beta-, 23 A-beta-, 11 A+beta+, and 51 A-beta+. Collectively, the two beta- groups differed from the two beta+ groups in earlier onset and longer duration of diabetes, lower body mass index, less glycemic improvement, and persistent insulin requirement. HLA class II genotyping showed that the A-beta- group differed from the A+beta- group in having lower frequencies of two alleles strongly associated with autoimmune type 1 diabetes susceptibility: DQA*03 and DQB1*02. Similarly, the A-beta+ group differed from the A+beta+ group in having a lower frequency of DQB1*02. Ketosis-prone diabetes comprises at least four etiologically distinct syndromes separable by autoantibody status, HLA genotype, and beta-cell functional reserve. Novel, nonautoimmune causes of beta-cell dysfunction are likely to underlie the A-beta+ and A-beta- syndromes.

[Factors associated with childhood diabetes manifesting as ketoacidosis and its severity]. / Facteurs associés à l'acidocétose révélatrice du diabète de l'enfant et à sa sévérité

INTRODUCTION: Type 1 diabetes in children in France is frequently diagnosed at the stage of ketoacidosis (DKA). PATIENTS AND METHODS: A prospective study was performed in a group of 72 children (mean age = 9.4 years) at onset of diabetes, in order to determine which factors were associated to DKA and to the severity of DKA (pH < 7.10) at diagnosis. RESULTS: Younger age was related to DKA (p = 0.03), but not to its severity. A lesser frequency of DKA was found in children with a family history of insulin-treated diabetes ( p = 0.04). Misdiagnosis was more frequently observed in children with DKA than in children without DKA (p = 0.02) and in case of severe DKA at admission by comparison with non severe cases (76 vs 23%; p = 0.002). Children in low economic intake families exhibited more frequently a severe DKA (77 vs 23%; p = 0.002) and were more frequently misdiagnosed before admission (48% vs 10%; p < 0.01). Urine strips for glucose and ketone determinations were underused for diagnosis before admission (15% only). CONCLUSION: Those results underline the need to both inform physicians and ameliorate the access to health care for low social class families, in order to take up the challenge of reducing the incidence of DKA at diagnosis in diabetic children in our country.

Using a severity of illness scoring system to assess intensive care unit admissions for diabetic ketoacidosis.

OBJECTIVE: To determine the appropriateness of intensive care unit (ICU) admissions for patients with the diagnosis of diabetic ketoacidosis (DKA) at our institution. DESIGN: Retrospective chart review. SETTING: Tertiary care inner-city hospital. SUBJECTS: All subjects admitted to the medical intensive care unit (MICU) from September 1996 to June 1997 with a diagnosis of DKA were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A grading system for the severity of DKA (grades 0-IV) from a previously published work was modified. Admissions to the MICU that were deemed appropriate a priori included patients with grade III or IV DKA, patients with grade II DKA who were older than 65 yrs of age, or patients with special situations normally warranting intensive care. MAIN RESULTS: Sixty-seven cases of DKA were reviewed. Two thirds of the patients had type I diabetes mellitus, and approximately 50% were men. No deaths occurred. Forty-four patients (66%) met the a priori ICU admission criteria. The average hospital stay for all patients was 4.2 (+/-3.6) days. The mean ICU stay was significantly longer in those with DKA grade III or IV, although the total hospital stay did not differ by severity of illness score. CONCLUSIONS: One third of the patients admitted to our MICU to receive treatment for DKA did not warrant ICU treatment based on the admission criteria. These individuals had an approximate MICU length of stay of 1 day. A prospective study of the severity of illness score will be undertaken to evaluate the safety, validity, and potential resource savings of applying these DKA ICU admission criteria within our institution.

Incidence and severity of ketoacidosis in childhood-onset diabetes in Kuwait. Kuwait Diabetes Study Group.

In 1992, the diabetes registry was started in Kuwait, as part of DiaMond, a WHO multinational collaborative project on the incidence of childhood-onset diabetes. Children (243) aged below 15 years, were identified between 1 January 1992 and 31 December 1995. Children (203) were Kuwaiti and 40 were non-Kuwaiti children but resident of Kuwait. For the years 1992, 1993, the annual incidence of childhood onset diabetes for Kuwaiti children was 15.4 per 100,000 (95% confidence interval 12.9-19), and the degree of ascertainment was 92%. Polyuria, polydypsia, weight loss and nocturia were the most frequently reported symptoms; four children were in coma and one in shock at presentation. Nearly half of the children (49%) presented ketoacidosis (venous pH < 7.3 and/or plasma bicarbonate level < 18 mmol/l). and in 53 children (23.5%) it was severe (venous pH < 7.1 and/or plasma bicarbonate level < 10 mmol/l). In 62 children (25.5%) it was mild to moderate (venous pH 7.1-7.3 and/or plasma bicarbonate level 10.1-18 mmol/l). The incidence of severe ketoacidosis was similar in all age groups and sexes. All children recovered completely without major complications and no deaths were recorded. We conclude that diabetic ketoacidosis is a common presentation at the onset of diabetes in childhood in Kuwait and attests to the lack of awareness of general practitioners and parents to the symptoms and signs of diabetes in childhood.

Evaluación del nivel de conocimiento sobre diabetes en pacientes y familiares atendidos en el Ambulatorio Urbano Tipo I "El Olivo"-Barquisimeto 1991-1994 / Evaluation of level Knowlege upper diabetes in patients and family attendend in urban ambulatory Tipe I \"El olivo\"-Barquisimeto 1991-1994

En el ambulatorio urbano tipo I "El Olivo", se realizó un estudio con el propósito de evaluar el nivel de conocimiento sobre Diabetes Mellitus que tienen pacientes y familiares, determinar la edad y sexo de los pacientes, señalar el nivel el nivel de información en cuanto a síntomas, complicaciones y su prevención, dieta, tratamiento y generalidades y relacionar el grado de instrucción y el nivel de conocimientos. Se encuestaron 40 pacientes y 40 familiares que acudieron a la Consulta de medicina interna. Se encontró que el 92,50 por ciento de los entrevistados pertenecen al sexo femenino, con un mayor número de individuos comprendida en el intervalo 51-60 años. En cuanto a la evaluación a las áreas del conocimiento se encontró que el nivel de instrucción de los pacientes fue para sintomatología regular (35 por ciento), para complicación y prevención regular (45 por ciento), para la categoría dieta el 70 por ciento osciló entre deficiente y malo, referente a tratamiento fue deficiente (42,40 por ciento) y generalidades, dicho conocimiento fue muy bueno (50 por ciento) y para familiares se encontró que en cuanto a sintomatología fue regular (35 por ciento), complicaciones y prevención malo (37,50 por ciento), conocimientos dietéticos fueron malos (62,50 por ciento), para tratamiento fue regular (47,50 por ciento) y para generalidades fue bueno (37,50 por ciento). Al relacionar el grado de instrucción y el nivel de conocimientos sobre Diabetes Mellitus de los pacientes se encontró que el 57,5 por ciento de los mismos son analfabetas de los cuales el 47,83 por ciento obtuvo un nivel de conocimentos deficiente, mientras que le 50 por ciento de individuos con educación secundaria incompleta

Use of PRISM scores in triage of pediatric patients with diabetic ketoacidosis.

Triage guidelines are needed to help in the decision process of intensive care unit (ICU) versus non-ICU admission for patients with diabetic ketoacidosis (DKA). Pediatric risk of mortality (PRISM) scores have long been used to assess mortality risk. This study assess the usefulness of the traditional PRISM score and adaptation of that score (PRISM-ED, which uses presentation data only) in predicting hospital stay in pediatric patients with DKA. PRISM and PRISM-ED were tested for correlation with length of stay and length of ICU stay. A medical record review was conducted for patients admitted to The Children's Hospital of Alabama with DKA during an 18-month period (n = 79). Two scores were calculated for each study entrant: PRISM using the worst recorded values over the first 24 hours and PRISM-ED using arrival values. Median scores, median test, and Spearman rank correlations were determined for both tests. Median PRISM scores were PRISM = 11 and PRISM-ED = 12; Median PRISM and PRISM-ED scores for patients admitted to the ICU were less than median scores among floor-admitted patients: [table: see text] Spearman rank correlations were significant for both scores versus total stay: PRISM, rs = 0.29; P = 0.009; PRISM-ED, rs = 0.60, P < 0.001. Also, correlations were significant for both scores versus ICU stay: PRISM rs = 0.22, P = 0.05; PRISM-ED, rs = 0.41, P < 0.001. Triage guidelines for ICU versus floor admission for DKA patients could have significant economic impact (mean ICU charge = $11,417; mean charge for floor admission = $4,447). PRISM scores may be an important variable to include in a multiple regression model used to predict the need for ICU monitoring.