Type 1 diabetes onset in children and adolescents: Clinical and temporal analysis in a tertiary referral center.

Aims: We aimed to analyze incidence and characteristics of patients with diabetic ketosis (DK) and diabetic ketoacidosis (DKA) in Caucasian adults with type 2 diabetes mellitus (T2DM). Methods: Studied population included 261, 749 adults. DK criteria included plasma glucose >13.9 mmol/L and ketonuria >2, while in DKA bicarbonate <18 mEq/L or pH<7.30 was also required. Hyperglycemic crises without these criteria were defined as non-ketotic hyperglycemia (NKH). Results: During a 5-year period, we observed 630 episodes of DK and 215 episodes of DKA. Only 8.6% of DK episodes and 34.4% of DKA were attributed to type 1 diabetes mellitus (T1DM). Patients with T1DM were younger, leaner, majority had newly diagnosed disease, and hyperglycemia was the main cause of admission. Standardized incidence ratio for DK was 48.1 (95% confidence interval [CI] 44.5-52.1) and 17.0 (95% CI 14.9-19.4) for DKA. Incidence for both DK and DKA was increasing with age. In patients younger than 50, the incidence of DK and DKA was similar. However, dramatic rise in the incidence of DK was observed in both sexes after the age of 50. When compared with patients with NKH, the patients with DK had higher serum pH and bicarbonates. Patients with T2DM had a risk of 0.8% for developing DKA and 2.9% for DK over 5- year period. Conclusions: Our study showed that DK and DKA are not uncommon in Caucasian adults and the majority of episodes were contributed to T2DM. Incidence of DK is far more higher than the incidence of DKA in patients older than 50, who predominantly have T2DM. Moreover, patients with DK have higher serum pH and bicarbonates, both of which imply that DK and DKA are distinct clinical entities in patients with T2DM. Further studies are needed to assess the impact of these clinical entities.

Aims: We aimed to analyze incidence and characteristics of patients with diabetic ketosis (DK) and diabetic ketoacidosis (DKA) in Caucasian adults with type 2 diabetes mellitus (T2DM).&#13;\n&#13;\nMethods: Studied population included 261,749 adults. DK criteria included plasma glucose &gt;13.9 mmol/L and ketonuria &gt;2, while in DKA bicarbonate &lt;18 mEq/L or pH&lt;7.30 was also required. Hyperglycemic crises without these criteria were defined as non-ketotic hyperglycemia (NKH).&#13;\n&#13;\nResults: During a 5-year period, we observed 630 episodes of DK and 215 episodes of DKA. Only 8.6% of DK episodes and 34.4% of DKA were attributed to type 1 diabetes mellitus (T1DM). Patients with T1DM were younger, leaner, majority had newly diagnosed disease, and hyperglycemia was the main cause of admission. Standardized incidence ratio for DK was 48.1 (95% confidence interval [CI] 44.5-52.1) and 17.0 (95% CI 14.9-19.4) for DKA. Incidence for both DK and DKA was increasing with age. In patients younger than 50, the incidence of DK and DKA was similar. However, dramatic rise in the incidence of DK was observed in both sexes after the age of 50. When compared with patients with NKH, the patients with DK had higher serum pH and bicarbonates. Patients with T2DM had a risk of 0.8% for developing DKA and 2.9% for DK over 5-year period.&#13;\n&#13;\nConclusions: Our study showed that DK and DKA are not uncommon in Caucasian adults and the majority of episodes were contributed to T2DM. Incidence of DK is far more higher than the incidence of DKA in patients older than 50, who predominantly have T2DM. Moreover, patients with DK have higher serum pH and bicarbonates, both of which imply that DK and DKA are distinct clinical entities in patients with T2DM. Further studies are needed to assess the impact of these clinical entities.

1. Justin M. Gregory, MD* 2. Daniel J. Moore, MD, PhD† 3. Jill H. Simmons, MD‡ 1. *Pediatric Endocrinology Clinical Fellow, Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, TN. 2. †Assistant Professor of Pediatrics, Assistant Professor of Pathology, Microbiology, and Immunology, Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, TN. 3. ‡Assistant Professor of Pediatrics, Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, TN. * ADA: : American Diabetes Association DKA: : diabetic ketoacidosis HbA1c: : glycosylated hemoglobin I:C ratio: : insulin-to-carbohydrate ratio IV: : intravenous TDD: : total daily dose T1DM: : type 1 diabetes mellitus T2DM: : type 2 diabetes mellitus 1. All children with type 1 diabetes mellitus (T1DM) should have their blood sugar managed with basal-bolus insulin treatment by either multiple daily injections or an insulin pump. 2. All children with T1DM should have access to a pediatric endocrinologist with a diabetes management team with resources to support patients and families. 3. All children with T1DM should be monitored for symptoms and/or screened for commonly associated conditions such as thyroid and celiac disease. After completing this article, readers should be able to: 1. Recognize the presenting signs and symptoms of type 1 diabetes mellitus (T1DM). 2. Know the key principles of effective diabetes self-management and the diabetes care team’s role in facilitating effective self-management. 3. Know the acute and chronic complications of (T1DM). 4. Identify how different categories of insulin analogues are used in daily insulin regimens. True, it is a fight, but there is pleasure in the struggle. Victory comes to the courageous; and without courage and common sense, success awaits no one. I look upon the diabetic as charioteer and his chariot as drawn by three steeds named Diet, Insulin, and Exercise. It takes skill to drive one horse, intelligence to manage a team of two, but a man must be a very good teamster who can get all three to pull together.EP Joslin, 1933 Type 1 diabetes mellitus (T1DM) is a disorder of glucose homeostasis characterized by autoimmune destruction of the insulin-producing pancreatic β-cell that progressively leads to insulin deficiency and resultant hyperglycemia. If left untreated, insulin deficiency leads to progressive metabolic derangement, with worsening hyperglycemia, ketoacidosis, starvation, and death. In …

Type 1 Diabetes Mellitus

There has been little change in the incidence of diabetic ketoacidosis (DKA) in newly diagnosed type 1 diabetes mellitus (T1DM) in children and adolescents in most developed countries. To assess potentially modifiable antecedents of DKA in children <15 years of age with new onset T1DM. Retrospective review of prospectively collected data from a complete regional cohort of children with T1DM in Auckland (New Zealand) from 2010 to 2014. DKA and severity were defined according to the ISPAD 2014 guidelines. A total of 263 children presented with new onset T1DM during the 5-year study period at 9.0 years of age (range 1.0-14.7), of whom 61% were NZ-European, 14% Maori, 13% Pacifica, and 11% other. A total of 71 patients (27%) were in DKA, including 31 mild, 20 moderate, and 20 severe DKA. DKA was associated with no family history of T1DM, higher glycated hemoglobin (HbA1c) values at presentation, self-presenting to secondary care, health care professional contacts in the 4 weeks before final presentation, and greater deprivation. Although a delay in referral from primary care for laboratory testing was common (81/216), only delay for more than 48 hours was associated with increased risk of DKA (11/22 > 48 h vs 12/59 referred at <48 h, P = .013). These data suggest that in addition to lack of family awareness potentially modifiable risk factors for new onset DKA include prolonged delay for laboratory testing and a low index of medical suspicion for T1DM leading to delayed diagnosis.

ObjectivesTo analyze clinical characteristics of children and young people (CYP) with T2DM presenting with DKA over a 3-year period in a DGH. Comparison of clinical characteristics of this group with...

Background: Some studies suggest that the SARS-CoV-2 pandemic increased the incidence of type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). However, the impact of this pandemic on pediatric T1DM is still mostly unknown. Therefore, we aimed to assess the effect of the COVID-19 pandemic on clinical outcomes in children with T1DM. Methods: We systematically searched for six databases up to 31 August 2022. We included 46 observational studies, 159,505 children of both sexes with T1DM, and 17,547 DKA events. Results: The COVID-19 pandemic significantly increased, in both sexes, the incidence of 1) DKA (OR 1.68; 95% CI 1.44–1.96), 2) severe DKA (OR 1.84; 95% CI 1.59–2.12), 3) DKA in newly diagnosed T1DM (OR 1.75; 95% CI 1.51–2.03), and 4) ICU admissions (OR 1.90; 95% CI 1.60–2.26). However, we did not find a significant association between this pandemic and 1) the incidence of T1DM, 2) the incidence of DKA in established T1DM, 3) the incidence of KDA complications, 4) the length of hospitalization stay, and 5) mortality. Subgroup analysis showed that the study design and the continent of origin accounted for the heterogeneity. Conclusions: The pandemic SARS-CoV-2 raised, in both sexes, the risk of DKA, severe DKA, DKA de novo, and ICU admissions.

Background: Some studies suggest that the SARS-CoV-2 pandemic increased the incidence of type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis (DKA). However, the impact of this pandemic on pediatric T1DM is still mostly unknown. Therefore, we aimed to assess the effect of the COVID-19 pandemic on clinical outcomes in children with T1DM. Methods: We systematically searched for six databases up to 31 August 2022. We included 46 observational studies, 159,505 children of both sexes with T1DM, and 17,547 DKA events. Results: The COVID-19 pandemic significantly increased, in both sexes, the incidence of 1) DKA (OR 1.68; 95% CI 1.44-1.96), 2) severe DKA (OR 1.84; 95% CI 1.59-2.12), 3) DKA in newly diagnosed T1DM (OR 1.75; 95% CI 1.51-2.03), and 4) ICU admissions (OR 1.90; 95% CI 1.60-2.26). However, we did not find a significant association between this pandemic and 1) the incidence of T1DM, 2) the incidence of DKA in established T1DM, 3) the incidence of KDA complications, 4) the length of hospitalization stay, and 5) mortality. Subgroup analysis showed that the study design and the continent of origin accounted for the heterogeneity. Conclusions: The pandemic SARS-CoV-2 raised, in both sexes, the risk of DKA, severe DKA, DKA de novo, and ICU admissions.

To understand the existing literature on the epidemiology and clinical, humanistic, and economic burden of diabetic ketoacidosis (DKA) in people living with type 2 diabetes mellitus (T2DM). MEDLINE, Embase and the Cochrane library were systematically searched for studies published between 1 January 2014 and 14 December 2023. Clinical trials and observational studies, conducted in people living with T2DM, were included if they provided data on DKA epidemiology, morbidity, mortality, hospitalizations or patient-reported outcomes. Studies of DKA-associated costs in T2DM were also included. Data were summarized descriptively. Overall, 197 publications were included. We found wide variations in DKA prevalence (0.0%-50.0%; 5th-95th percentile: 0.02%-26%; 126 publications) and incidence (0.0-24.5 events per 1000 patient years; 5th-95th percentile: 0.004-7.6 events per 1000 patient years; 37 publications). Populations at increased risk of DKA included patients using sodium-glucose cotransporter-2 inhibitors, those using insulin and those with poor glycaemic control. The most common precipitating factors were infection and non-adherence to treatment. There was limited evidence on the humanistic burden of DKA, but the results highlighted a high burden of complications including acute kidney injury or failure. The length of hospital stay ranged from days to several weeks. DKA is associated with a high clinical burden in people living with T2DM. Resources to screen for and potentially prevent DKA may reduce the burden of DKA for patients with T2DM and the healthcare system.

This study characterized incidence, patient profiles, risk factors and outcomes of in-hospital diabetic ketoacidosis (DKA) in patients with COVID-19 compared with influenza and pre-pandemic data. This study consisted of 13 383 hospitalized patients with COVID-19 (March 2020-July 2022), 19 165 hospitalized patients with influenza (January 2018-July 2022) and 35 000 randomly sampled hospitalized pre-pandemic patients (January 2017-December 2019) in Montefiore Health System, Bronx, NY, USA. Primary outcomes were incidence of in-hospital DKA, in-hospital mortality, and insulin use at 3 and 6 months post-infection. Risk factors for developing DKA were identified. The overall incidence of DKA in patients with COVID-19 and influenza, and pre-pandemic were 2.1%, 1.4% and 0.5%, respectively (p < .05 pairwise). Patients with COVID-19 with DKA had worse acute outcomes (p < .05) and higher incidence of new insulin treatment 3 and 6 months post-infection compared with patients with influenza with DKA (p < .05). The incidence of DKA in patients with COVID-19 was highest among patients with type 1 diabetes (12.8%), followed by patients with insulin-dependent type 2 diabetes (T2D; 5.2%), non-insulin dependent T2D (2.3%) and, lastly, patients without T2D (1.3%). Patients with COVID-19 with DKA had worse disease severity and higher mortality [odds ratio = 6.178 (4.428-8.590), p < .0001] compared with those without DKA. Type 1 diabetes, steroid therapy for COVID-19, COVID-19 status, black race and male gender were associated with increased risk of DKA. The incidence of DKA was higher in COVID-19 cohort compared to the influenza and pre-pandemic cohort. Patients with COVID-19 with DKA had worse outcomes compared with those without. Many COVID-19 survivors who developed DKA during hospitalization became insulin dependent. Identification of risk factors for DKA and new insulin-dependency could enable careful monitoring and timely intervention.

Objective To summarize the clinical features of diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes mellitus(T1DM), and to explore the predictors of DKA by analyzing these factors in order to achieve early recognition. Methods In this retrospective study, 200 children with newly-onset T1DM from January 2009 to December 2012 in Shengjing Hospital of China Medical University were chosen.These patients were divided into DKA group and non-DKA group.Clinical data including age, gender, health insurance, body shape, infection history, family history of diabetes, type of residence, income, duration of history, C peptide, glycosylated hemoglobin, blood lipids, thyroid tests, diabetes antibodies etc were collected. Results Among 200 cases of newly diagnosed T1DM, 107 children had DKA, 93 children had non-DKA, and the incidence of DKA was 53.5%.In the group of DKA, 39 cases (36.5%) were male, 68 cases were female, while in the group of non-DKA 45 cases (48.4%) were male, 48 cases were female.In the group of DKA, children ranged in age from 16 months to 13 years old, and the average age was (6.53±3.55) years old.In the non-DKA group, children ranged in age from 1 to 14 years old, and the average age was (7.05±3.55)years old.In the group of DKA, 43 cases (40.2%) didn't have health insurance, while in the non-DKA group, 28 cases (30.1%) didn't have medical insurance.In the DKA group, 30 cases (28%) had a family history of diabetes, while in the non-DKA group, 27 cases (29%) had a family history of diabetes.In the group of DKA, the duration was (30.24±76.50 )days, while in the group of non-DKA, the duration was (33.38±49.30) days.The glycosylated hemoglobin in the DKA group was (12.38±2.66)%, in the non-DKA group was (12.48±2.24)%.There were no significantly differences of the above factors between the 2 groups(all P>0.05). In the group of DKA, 35 cases(32.7%) were thin, 66 cases(61.7%) were of normal size, and 6 cases(5.6%) were fat.In the group of non-DKA, 9 cases(9.3%) were thin, 76 cases (78.6%) were of normal size, and 8 cases(12.1%) were fat.In the group of DKA, 33 cases(30.8%) had infection history, 77 cases(72%) lived in rural areas, and the average of C peptide was (0.25±0.22) μg/L.In the group of non-DKA, 17 cases(18.3%) had infection history, 52 cases(55.9%) in rural areas, and the average of C peptide was (0.36±0.21) μg/L.There were significant differences of the above factors between the 2 groups(all P<0.05). Conclusions Children with newly diagnosed T1DM who is thin, rural resident, and has lower C peptide level is more susceptible to DKA.More attention should be paid to the children with newly diagnosed T1DM who have above characteristics. Key words: Type 1 diabetes mellitus; Diabetic ketoacidosis; Affect factor; Child

Background A wide range of reports on the incidence of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in children have been published worldwide. Reports from Saudi Arabia are limited. The aim of this study was to assess the incidence, clinical pattern and severity of DKA in children with newly diagnosed T1DM and the association of autoimmune conditions with initial DKA occurrence at King Abdulaziz Medical City - Jeddah. Methods This retrospective chart review was conducted during the period 2005-2015. All newly diagnosed T1DM children during the study period were investigated (n = 390). Data were collected on the demographic characteristics, body mass index (BMI), DKA severity, length of hospital stay and follow-up data on the type of diabetes therapy. Results The incidence of DKA among newly diagnosed T1DM pediatric patients was 37.7% (n = 147). Moderate and severe DKA cases were significantly higher among female children (p = 0.04). Patients diagnosed with DKA had lower BMI (20.87 ± 5.21) than their counterparts (p = 0.03). The median length of hospital stay was higher among severe DKA compared to moderate and mild cases (5.0, 4.5 and 4.0 days, respectively). Conclusions The incidence of DKA among newly diagnosed T1DM is still high compared to developed countries; however, it is relatively lower than previous reports in Saudi Arabia. Immediate interventions, such as awareness campaigns, are vital to reduce the burden of this preventable health sequela among children with DM.

Background: Diabetic ketoacidosis and hyperosmolar hyperglycemic non-ketotic coma (HHNK) are two serious acute complications of diabetes mellitus. DKA consists of the biochemical triad of hyperglycemia, ketonemia and acidemia. In DKA and HHNK dehydration and sodium depletion is seen. Lack of insulin causes hyperglycemia and also inhibits entry of potassium into the cells leading to hyperkalemia. Moreover Hyperglucagonemia also contributes to hyperglycemia and can worsen the diabetic state. Study Design: This study was retrospective, analytical case control study. Non - probability convenient sampling technique was used. Materials and Methods: We reviewed the hospital admissions and patients coming to OPD with type1 & 2 diabetes mellitus as well as diabetic complications like diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic non-ketotic coma (HHNK). We compared the groups for plasma glucose, plasma osmolality, plasma glucagon, serum electrolytes and arterial blood gases (ABGs) with control group. Results: Twelve persons were considered as control being non-diabetic with normal oral glucose tolerance. Mean plasma glucose level & mean plasma osmolality level in the patients of uncontrolled type 2 diabetes mellitus, uncontrolled type I diabetes mellitus, DKA and HHNK was significantly higher (p < 0.001) as compared with control subjects. Mean plasma glucagon level in the patients of uncontrolled type I diabetes mellitus and DKA was found significantly higher (p < 0.001) as compared with control subjects. Serum potassium level was significantly higher in patients of uncontrolled type 2 diabetes mellitus, uncontrolled type 1 diabetes mellitus, HHNK (p <0.001) and DKA (p <0.01) as compared with control subjects. Arterial pH was significantly lower in patients of DKA (p < 0.001), uncontrolled type 1 diabetes mellitus (p < 0.05) and HHNK (p < 0.01). Arterial PCO 2 was significantly lower in patients of DKA (p < 0.05). Plasma bicarbonate levels were found significantly lower in patients of DKA (p < 0.001) and HHNK (p < 0.01). Discussion: The present study showed that in type 1 DM hyperglucagonemia was more marked leading to excessive ketone bodies production and resulting in DKA. The ketoacids formed during DKA are strong acids that fully dissociate at physiological pH. So ketonuria lead to excretion of positively charged cations (Na + , K + , NH 4 + ). Moreover, the hydrogen ions were titrated by plasma bicarbonate ions, resulting in metabolic acidosis and retention of anions lead to increase in the plasma anion gap in DKA. The degree of hyperosmolality and hyperglycemia was more marked in patients with HHNK as compared with DKA. The osmotic effects of glycosuria resulted in impairment reabsorption of NaC1 and H 2 O and ultimately hyponatremia. Whereas Serum potassium level was found to be significantly higher in uncontrolled type I diabetes mellitus, uncontrolled type 2 diabetes mellitus, DKA and HHNK. These observations were according to the results of previous studies. Conclusions: Hyperglucagonemia causes marked hyperglycemia under conditions of relative insulin deficiency and can worsen the diabetic state like development of DKA when insulin deficiency becomes absolute as in type 1 diabetes mellitus. Key words: Diabetes mellitus (DM), diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic non-ketotic coma (HHNK), arterial blood gases (ABGs), plasma osmolality.

History with type 2 diabetes mellitus (T2DM) is manifested by the presence of insulin resistance and β-cell dysfunction which prerequisites for T2DM development involving unbalanced energy intake and expenditure. Uncoupling gene protein 2 is the main regulator of energy balance. This study aims to determine the UCP2 -866G/A genetic variation in obese individuals with a family history of T2DM and without a family history of T2DM. The study was a case control design in which the case subjects (n = 60) were obese individuals with a family history of T2DM and control subjects (n = 60) without a family history of T2DM. Polymorphism was analyzed with PCR-RFLP. The value of HOMA-IR and HOMA-β was calculated by the HOMA formula. Data was analyzed by Independent Sample t-test, Mann Whitney U-test, Chi-Square test and Kruskal-Wallis test with a significance level of p &lt; 0.05. The frequency of genotype and alleles in obese individuals with a family history of T2DM and without a history of T2DM did not differ significantly, GA+AA (56.7 %) and A (32.5 %) allele was higher in individuals with a family history of T2DM. The GG+AA genotype in the male group with a family history of T2DM could significantly increase the risk of UCP2 gene polymorphism in T2DM by 2.23 times (CI 95 % 0.64 - 8.14) whereas in the female group there was no risk of T2DM. HOMA-IR and HOMA-β value in both family background did not differ significantly. The value of HOMA-β in the female gender group had significant relationship between obese individuals with a family history of T2DM (p = 0.04). Conclusion: The result suggests obese individuals with a family history of T2DM have a higher risk of getting GA+AA genotypes and A allele than individuals without a family history of T2DM.&#x0D; HIGHLIGHTS&#x0D; &#x0D; Energy intake that exceeds energy expenditure will cause body fat mass to increase when a state of positive energy balance occurs&#x0D; The genetic component for obesity is associated with relative risks between family relationships and body composition relationships&#x0D; The obese individuals with a family history of T2DM have a higher risk of GA + AA genotype and A allele than individuals without a family history of T2DM&#x0D; &#x0D; GRAPHICAL ABSTRACT

“The Proof is in the Pudding”: Do SGLT2 Inhibitors Cause Diabetic Ketoacidosis?