Multicentre, retrospective cohort study protocol to identify racial and ethnic differences in acute kidney injuries in children and adolescents with diabetic ketoacidosis.

INTRODUCTION: Approximately 40% of children with diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), which increases the risk of chronic kidney damage. At present, there is limited knowledge of racial or ethnic differences in diabetes-related kidney injury in children with diabetes. Understanding whether such differences exist will provide a foundation for addressing disparities in diabetes care that may continue into adulthood. Further, it is currently unclear which children are at risk to develop worsening or sustained DKA-related AKI. The primary aim is to determine whether race and ethnicity are associated with DKA-related AKI. The secondary aim is to determine factors associated with sustained AKI in children with DKA. METHODS AND ANALYSIS: This retrospective, multicentre, cross-sectional study of children with type 1 or type 2 diabetes with DKA will be conducted through the Paediatric Emergency Medicine Collaborative Research Committee. Children aged 2-18 years who were treated in a participating emergency department between 1 January 2020 and 31 December 2023 will be included. Children with non-ketotic hyperglycaemic-hyperosmolar state or who were transferred from an outside facility will be excluded. The relevant predictor is race and ethnicity. The primary outcome is the presence of AKI, defined by Kidney Disease: Improving Global Outcomes criteria. The secondary outcome is 'sustained' AKI, defined as having AKI ≥48 hours, unresolved AKI at last creatinine measurement or need for renal replacement therapy. Statistical inference of the associations between predictors (ie, race and ethnicity) and outcomes (ie, AKI and sustained AKI) will use random effects regression models, accounting for hospital variation and clustering. ETHICS AND DISSEMINATION: The Institutional Review Board of Children's Minnesota approved this study. 12 additional sites have obtained institutional review board approval, and all sites will obtain local approval prior to participation. Results will be presented at local or national conferences and for publication in peer-reviewed journals.

Inequities in Diabetic Ketoacidosis Among Patients With Type 1 Diabetes and COVID-19: Data From 52 US Clinical Centers.

OBJECTIVE: We examined whether diabetic ketoacidosis (DKA), a serious complication of type 1 diabetes (T1D) was more prevalent among Non-Hispanic (NH) Black and Hispanic patients with T1D and laboratory-confirmed coronavirus disease 2019 (COVID-19) compared with NH Whites. METHOD: This is a cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 52 clinical sites in the United States, data were collected from April to August 2020. We examined the distribution of patient factors and DKA events across NH White, NH Black, and Hispanic race/ethnicity groups. Multivariable logistic regression analysis was performed to examine the odds of DKA among NH Black and Hispanic patients with T1D as compared with NH White patients, adjusting for potential confounders, such as age, sex, insurance, and last glycated hemoglobin A1c (HbA1c) level. RESULTS: We included 180 patients with T1D and laboratory-confirmed COVID-19 in the analysis. Forty-four percent (n = 79) were NH White, 31% (n = 55) NH Black, 26% (n = 46) Hispanic. NH Blacks and Hispanics had higher median HbA1c than Whites (%-points [IQR]: 11.7 [4.7], P < 0.001, and 9.7 [3.1] vs 8.3 [2.4], P = 0.01, respectively). We found that more NH Black and Hispanic presented with DKA compared to Whites (55% and 33% vs 13%, P < 0.001 and P = 0.008, respectively). After adjusting for potential confounders, NH Black patients continued to have greater odds of presenting with DKA compared with NH Whites (OR [95% CI]: 3.7 [1.4, 10.6]). CONCLUSION: We found that among T1D patients with COVID-19 infection, NH Black patients were more likely to present in DKA compared with NH White patients. Our findings demonstrate additional risk among NH Black patients with T1D and COVID-19.

Type 1 diabetes outcomes of children born in Israel of Eritrean asylum seekers.

AIMS: Disparities in health outcomes in pediatric type 1 diabetes (T1D) based on race/ethnicity and socioeconomic position (SEP) have been reported. We compared T1D characteristics between Eritrean status-less children living in Israel and native-born Israeli children. METHODS: This observational study compared 7 Eritrean and 28 Israeli children (< 8 years old at T1D diagnosis) who were diagnosed in a single diabetes center during 2015-2019. Sociodemographic and diabetes-related data from diagnosis until the last clinic visit were retrieved from their medical files. RESULTS: At diagnosis, the mean age was 4.8 ± 2.2 years, 17 (48.6%) had diabetic ketoacidosis with a mean HbA1c level of 10.5 ± 2.1% (91.3 mmol/mol) and 29 (82.9%) had ≥ 2 pancreatic autoantibodies. The mean T1D duration of follow-up was 2.7 ± 1.4 years. Overall glycemic control during follow-up (> 6 months from diagnosis, mean number of samples 10.6 ± 5.2) was good, with mean, best, and peak HbA1c levels of 7.4 ± 0.8% (57.4 mmol/mol), 6.7 ± 0.7% (49.7 mmol/mol), and 8.1 ± 1.1% (65 mmol/mol), respectively. Thirty-two children (91.4%) used continuous glucose monitoring devices (CGMs), and the mean time from diagnosis to CGM initiation was 10.8 ± 14.1 months. CGM metrics: time CGM active: 95.4 ± 3.8%, mean glucose level: 170.0 ± 27.0 mg/dl (9.4 mmol/L), time-in-range: 56.4 ± 14.7%, time-below-range: 5.5 ± 5.7%, and time-above-range: 38.6 ± 16.1%. Diabetes-related parameters at diagnosis and during follow-up were similar between groups. Eritrean children had significantly lower SEPs (P < 0.001) and parental education levels (P < 0.001). Correlations between SEP and diabetes parameters and SEP and growth parameters were not significant. CONCLUSIONS: Eritrean status-less children in Israel achieved glycemic targets similar to those of Israeli children, perhaps reflecting uniformity in the standard of care and CGM usage.

Racial/Ethnic Minority Youth With Recent-Onset Type 1 Diabetes Have Poor Prognostic Factors.

OBJECTIVE: To compare races/ethnicities for characteristics, at type 1 diabetes diagnosis and during the first 3 years postdiagnosis, known to influence long-term health outcomes. RESEARCH DESIGN AND METHODS: We analyzed 927 Pediatric Diabetes Consortium (PDC) participants <19 years old (631 non-Hispanic white [NHW], 216 Hispanic, and 80 African American [AA]) diagnosed with type 1 diabetes and followed for a median of 3.0 years (interquartile range 2.2-3.6). Demographic and clinical data were collected from medical records and patient/parent interviews. Partial remission period or "honeymoon" was defined as insulin dose-adjusted hemoglobin A1c (IDAA1c) ≤9.0%. We used logistic, linear, and multinomial regression models, as well as repeated-measures logistic and linear regression models. Models were adjusted for known confounders. RESULTS: AA subjects, compared with NHW, at diagnosis, were in a higher age- and sex-adjusted BMI percentile (BMI%), had more advanced pubertal development, and had higher frequency of presentation in diabetic ketoacidosis, largely explained by socioeconomic factors. During the first 3 years, AA subjects were more likely to have hypertension and severe hypoglycemia events; had trajectories with higher hemoglobin A1c, BMI%, insulin doses, and IDAA1c; and were less likely to enter the partial remission period. Hispanics, compared with NHWs, had higher BMI% at diagnosis and over the three subsequent years. During the 3 years postdiagnosis, Hispanics had higher prevalence of dyslipidemia and maintained trajectories of higher insulin doses and IDAA1c. CONCLUSIONS: Youth of minority race/ethnicity have increased markers of poor prognosis of type 1 diabetes at diagnosis and 3 years postdiagnosis, possibly contributing to higher risk of long-term diabetes complications compared with NHWs.

23 years of managing diabetic ketoacidosis at Auckland Hospital

AIMS: To examine the length of stay and need for intensive care of people admitted with diabetic ketoacidosis (DKA) to a single centre between 1988 and 2011. METHODS: Patients aged ≥15 years admitted for the first time with DKA (plasma glucose ≥ 10mmol/L and a bicarbonate concentration ≤15mmol/L and a pH <7.35, and raised plasma or urine ketones or anion gap) to Auckland City Hospital from 1988-2011 were identified retrospectively. The patients were divided into four cohorts (1988-1996; 1997-2001; 2002-2006; 2007-2011). Over this time period there was no significant change to the insulin infusion protocol. RESULTS: There were 576 admissions with DKA in 388 people over the 23 years. The mean age of the patients and glucose concentration at presentation to hospital fell significantly over time. The admission pH and bicarbonate concentration was higher in more recent cohorts. The length of stay and need for intensive care admission fell significantly over time, but the number of patients subsequently readmitted with DKA remained high. In-hospital mortality remained low. CONCLUSIONS: DKA remains an important reason for admission to this hospital, but the severity of DKA at presentation has reduced over time. The need for intensive care admission and length of stay has fallen dramatically.

Ketosis-prone atypical diabetes in Cameroonian people with hyperglycaemic crisis: frequency, clinical and metabolic phenotypes.

AIM: It is unclear whether ketosis-prone diabetes is a specific type or a subtype of Type 2 diabetes. We aimed to describe the clinical and metabolic features of ketosis-prone diabetes in a sub-Saharan population. METHODS: We consecutively enrolled and characterized 173 people with non-autoimmune diabetes admitted for hyperglycaemic crisis at the Yaoundé Central Hospital, Cameroon. Blood samples were collected for fasting glucose, HbA1c , lipid profile and C-peptide assays with insulin resistance and secretion estimation by homeostasis model assessment. People were classified as having Type 2 diabetes (n = 124) or ketosis-prone diabetes (n = 49). Ketosis-prone diabetes was sub-classified as new-onset ketotic phase (n = 34) or non-ketotic phase (n = 15). RESULTS: Ketosis-prone diabetes was found in 28.3% of the hyperglycaemic crises. Age at diabetes diagnosis was comparable in Type 2 and ketosis-prone diabetes [48 ± 14 vs 47 ± 11 years; P = 0.13] with a similar sex distribution. Overall BMI was 27.7 ± 13.4 kg/m2 and was ≥ 25 kg/m2 in 55.8% of those taking part, however, 73.5% of those with ketosis-prone diabetes reported weight loss of > 5% at diagnosis. Blood pressure and lipid profile were comparable in both types. Ketosis-prone diabetes in the ketotic phase was characterized by lower insulin secretion and higher serum triglycerides compared with non-ketotic ketosis prone and Type 2 diabetes. Type 2 and ketosis prone diabetes in the non-ketotic phase were comparable in terms of lipid profile, blood pressure, waist-to-hip ratio, BMI and fat mass, insulin secretion and insulin resistance indices. CONCLUSIONS: Ketosis-prone diabetes is likely to be a subtype of Type 2 diabetes with the potential to develop acute insulinopenic episodes.

Usefulness of postmortem biochemistry in identification of ketosis: Diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition.

A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings.

Impact and characteristics of the non-Caucasian population in hospital admissions for diabetes onset during 2003-2010. / Impacto y características diferenciales de la población de origen no caucásico en los ingresos por inicio de diabetes durante el periodo 2003-2010.

AIMS: To assess the prevalence of non-Caucasian patients in hospital admissions for onset of symptomatic diabetes mellitus during the 2003-2010 period, and to analyze the characteristics differentiating them from the Caucasian population at diagnosis and 2 years later. MATERIAL AND METHODS: A retrospective, observational study. INCLUSION CRITERIA: Patients aged 18-40 years admitted for de novo symptomatic diabetes from January 2003 to October 2010. Prevalence of patients of non-Caucasian origin was analyzed, and clinical, biochemical, immunological, and beta-cell function of both populations were compared at diagnosis and 2 years later. RESULTS: Nineteen percent of patients admitted to hospital for de novo symptomatic diabetes were non-Caucasian, with a progressive increase in recent years. Non-Caucasian patients had milder decompensation (3.0% had ketoacidosis, as compared to 15.2% in the Caucasian group, P<.05), lower presence of autoimmunity (27.2 vs. 73.1%, P<.01) and higher stimulated C-peptide levels (0.70±0.56 vs. 0.42±0.39 nmol/l, P<.05), mainly because of the subgroup with negative autoimmunity (0.82 vs. 0.25). Two years after diagnosis, less non-Caucasian patients were on intensified treatment (39.1 vs. 93.8%). CONCLUSIONS: Non-Caucasian patients had a lower prevalence of autoimmunity, better beta-cell function at diagnosis, particularly due to the subgroup with negative autoimmunity, and less need for intensive treatment 2 years after diagnosis, features which are more characteristic of type 2 diabetes mellitus.

Impact of Maternal Country of Birth on Type-1-Diabetes Therapy and Outcome in 27,643 Children and Adolescents from the DPV Registry.

OBJECTIVE: To study the impact of maternal country of birth on type-1-diabetes (T1D) therapy and outcome. STUDY DESIGN AND METHODS: 27,643 T1D patients aged ≤20 years with documented maternal country of birth from the multicenter German/Austrian diabetes patient registry (DPV) were analyzed. Patients were categorized based on their mother's origin: Germany/Austria (reference), Turkey, Southern Europe, and Eastern Europe. To compare BMI standard deviation score (BMI-SDS), diabetes therapy and outcome between groups, multivariable regression was applied with adjustments for age, sex and duration of diabetes. Based on observed marginal frequencies, adjusted estimates were calculated. Linear regression was used for continuous data, logistic regression for binary data and Poisson regression for count data. All statistical analyses were performed using SAS 9.4. Significance was set at a two-tailed p<0.05. RESULTS: 83.3% of patients were offspring of native mothers. A Turkish, Southern or Eastern European background was documented in 2.4%, 1.7% and 4.3% of individuals. After demographic adjustment, patients with migration background had a higher mean BMI-SDS (Turkey, Southern Europe or Eastern Europe vs. Germany/Austria: 0.58±0.03, 0.40±0.04, or 0.37±0.02 vs. 0.31±0.01; ±SE) and a lower use of insulin pumps (26.8%, 27.9%, or 32.6% vs. 37.9%) compared to offspring of native mothers. Mean HbA1c was worst in individuals of Turkish mothers (Turkey vs. Germany/Austria: 69.7±0.7 vs. 66.6±0.1 mmol/mol; ±SE). Patients of Eastern European descent had an increased rate of severe hypoglycemia (22.09±0.13 vs. 16.13±0.02 events per 100 patient-years) and ketoacidosis was more prevalent in offspring of Turkish or Southern European mothers (7.50±0.10, or 7.13±0.11 vs. 6.54±0.02 events per 100 patient-years). Patients of Turkish descent were more often hospitalized (57.2±2.7 vs. 48.5±0.4 per 100 patient-years). All differences were significant. CONCLUSION: The differences in diabetes therapy and outcome among patients with distinct migration background suggest that specific challenges have to be considered in clinical care.

Increased risk of severe diabetic ketoacidosis among Jewish ultra-orthodox children.

AIMS: Diabetic ketoacidosis (DKA) at diabetes diagnosis is a dangerous yet potentially preventable condition. Young age, low socioeconomic status, and low parental education have been found to be associated with increased risk of DKA. We aimed to evaluate the impact of religious affiliation on presentation with DKA at type 1 diabetes mellitus (T1DM) diagnosis in Jewish children. METHODS: The study comprised an analysis of medical records of all consecutive patients with new-onset T1DM who were admitted to one tertiary medical center from January 2007 to January 2014. DKA was defined as venous pH <7.3 or HCO3(-) < 15 mmol/l, and severe DKA as pH <7.1 or HCO3(-) < 5 mmol/l. RESULTS: Of 81 patients with new-onset T1DM (38 females, mean ± SD age at diagnosis 9.9 ± 4.2 years), 34 (42 %) presented with DKA: 21 of 60 (35 %) of patients from secular families and 13 of 21 (62 %) from ultra-orthodox families. Children from ultra-orthodox families had a 3.5-fold increased risk of presenting with DKA than children from secular families (95 % CI 1.2-10.1, p = 0.02) and a 3.8-fold risk to be admitted with severe DKA (95 % CI 1.1-12.6, p = 0.02). Other factors that were found to be associated with an increased risk of DKA were younger age, an absence of maternal academic education, and residence in an area of low socioeconomic status. CONCLUSIONS: DKA and severe DKA at diabetes diagnosis were more common among religious ultra-orthodox than among secular Jewish children. Awareness of the symptoms and dangers of DKA in new-onset T1DM should be directed to particularly high-risk population groups.

[Differences in clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in Jewish and Bedouin patients].

BACKGROUND: The aim of this study was to compare clinical characteristics and outcomes of diabetic ketoacidosis (DKA) in the Jewish and Bedouin populations. METHODS: A retrospective analysis was conducted of hospital admissions for diabetic ketoacidosis in adult patients between 2003 and 2010. The clinical and biochemical characteristics and outcomes of diabetic ketoacidosis patients of Jewish origin were compared with those of Bedouin origin. The primary outcome was in-hospital all-cause mortality. RESULTS: The study cohort included 220 consecutive patients for whom the admission diagnosis was diabetic ketoacidosis. The cohort was categorized according to Jewish and Bedouin origin as follows: 177 (80.5%) Jewish and 43 (19.5%) Bedouin patients. The Jewish patients were significantly older than the Bedouin patients (45.8 +/- 18.9 vs. 32.9 +/- 15.3, p < 0.001). The majority of the patients with diabetic ketoacidosis in both the Jewish and Bedouin groups had type 1 diabetes mellitus. No differences were found for in-hospital mortality, 30 days mortality or complication rates in groups of Jewish and Bedouin patients. The Length of hospital stay was significantly Longer in the Jewish compared to the Bedouin groups of patients (median 4 days (IQR 2; 6 days) vs. median 3 days (IQR 2; 4 days) respectively, p = 0.05). CONCLUSIONS: We did not find significant differences in the outcomes between Bedouin and Jewish patients with diabetic ketoacidosis. The Bedouin patients in the present study were younger compared to Jewish patients and the Length of the hospital stay was shorter in the Bedouin compared to the Jewish group. Advanced age, mechanical ventilation and bed-ridden state were independent predictors of 30-day mortality in both ethnic groups.

Race, socioeconomic status, and treatment center are associated with insulin pump therapy in youth in the first year following diagnosis of type 1 diabetes.

BACKGROUND: Increasing numbers of children and adolescents with type 1 diabetes (T1D) have been placed on insulin pump therapy. Nevertheless, data are limited regarding patterns of pump use during the first year of treatment and the clinical and socioeconomic factors associated with early use of pump therapy. Therefore, we sought to determine factors associated with pump therapy within the first year of diagnosis in youth enrolled in the Pediatric Diabetes Consortium (PDC) T1D New-Onset (NeOn) Study. SUBJECTS AND METHODS: The NeOn Study includes youth <19 years old at T1D diagnosis who have been followed from the time of diagnosis at seven U.S. pediatric diabetes centers. Cox regression was used to determine factors associated with transition from injection to pump therapy during the first year of T1D in 1,012 participants. RESULTS: Twenty-seven percent (n=254) of participants began pump therapy within the first year of diagnosis, ranging from 18% to 59% among the seven centers. After adjusting for center effect, factors associated with pump use in multivariate analysis included private health insurance (37% vs. 7%; P<0.001), having annual household income over $100,000 (50% vs. 15%; P<0.001), and non-Hispanic white race (36% vs. 11%; P<0.001). The hemoglobin A1c level did not appear to influence the decision to initiate pump use. CONCLUSIONS: Participants of non-Hispanic white race and higher socioeconomic status were more likely to be placed on pumps during the first year. Further investigations are needed to gain a better understanding of barriers to use of pumps in youth with T1D, especially in disadvantaged and minority families.

Ethnic differences in glycemic control and diabetic ketoacidosis rate among children with diabetes mellitus type 1 in the Negev area.

BACKGROUND: The existent glycemic control of type 1 diabetes mellitus (T 1DM) patients in daily practice might not reach the goals determ ied in guidelines. Ethnic diversity was also shown to influence glycemic control. OBJECTIVES: To evaluate glycemic control, prevalence of diabetic ketoacidosis (DKA) at presentation, diabetic complications rate, and associated autoimmune diseases in a pediatric Ti M patient population in the Negev area. METHODS: Clinical and demographic details of 168 T1iDM patients were evaluated, including HbA1C levels, long-term complications, related autoimmune diseases, and insulin pump usage. The data were analyzed and the Jewish and Bedouin patient groups compared. RESULTS: Only 13.1% of the patients had reached the HbA1C levels recommended by the current guidelines at the first and second year follow-up visits, and 9.5% and 7.1% at the third and fourth year visits, respectively. A significant difference in HbAlc levels between Jewish and Bedouin patients was found (P = 0.045 at the first year follow-up, P 0.01 thereafter). Significant difference was found between the Jewish and the Bedouin groups regarding presentation with DKA, 33% and 56% of the patients respectively (P= 0.01). CONCLUSIONS: Existent glycemic control in daily practice is far from the guideline goals. Bedouin ethnicity was associated with less favorable diabetes control, emphasizing the need for better awareness of T1DM and its treatment options in this population. More resources should be directed to address T1DM in the general population, especially among the Bedouin.

Islet immunity and beta cell reserve of indigenous Black South Africans with ketoacidosis at initial diagnosis of diabetes.

OBJECTIVE: Islet immunity and beta cell reserve status were utilized to classify persons with ketoacidosis as the initial manifestation of diabetes. The clinical features of the various diabetes classes were also characterized. DESIGN: Prospective cross sectional study. SETTING: Nelson Mandela Academic Hospital, Mthatha, Eastern Cape Province, South Africa. PATIENTS: Indigenous Black South Africans with ketoacidosis as the initial manifestation of diabetes. INTERVENTIONS: Islet immunity and beta cell reserve were respectively assessed using serum anti-glutamic acid decarboxylase 65 (GAD) antibody and serum C-peptide after 1 mg of intravenous glucagon. OUTCOME MEASURES: Serum anti-GAD 65 antibody > or = 5 units/L and < 5 units/L, respectively defined anti-GAD 65 positive (A+) and negative (A-). Replete (beta+) and deplete (beta-) beta cell reserve were serum C-peptide after glucagon injection of > or = 0.5 ng/mL and < 0.5 ng/mL, respectively. The proportions of patients with A+beta-, A+beta+, A-beta- and A-beta+ and their clinical characteristics were determined. RESULTS: Of the 38 males and 33 females who participated in the study, patients were categorized in various classes: A-beta+, 46.5% (n=33/ 71); A-beta-, 26.8% (n=19/71); A+beta-, 22.5% (n=16/71); and A+beta+, 4.2% (n=3/71). The ages of the various classes were: 41.8 +/- 13.8 years for A-beta+ (n=33); 36.5 +/- 14.6 years for A-beta- (n=19); and 20.6 +/- 7.1 years for the combination of A+beta- with A+beta+ (n=19) (P<.0001, P<.0001 for the combination of A+beta- and A+beta+ vs A-beta+, P=.001 for the combination of A+beta- and A+beta+ vs A-beta-and P=.2 for A-beta- vs A-beta+. The clinical features of type 2 diabetes were most prevalent in A-beta+ class while the A+beta- and A+beta+ groups had the clinical profile of type 1A diabetes. CONCLUSIONS: Most of the indigenous Black South African patients with ketoacidosis as the initial manifestation of diabetes had islet immunity, beta cell reserve status and clinical profiles of type 2 diabetes.

Clinical analysis of fulminant type 1 diabetes in China and comparison with a nationwide survey in Japan.

OBJECTIVES: To report 26 cases of fulminant type 1 diabetes found in Guangdong Medical College Futian Hospital and Central South University Second Xiangya Hospital in China and to study the difference between Chinese and Japanese patients. METHODS: The clinical and biochemical characteristics of 26 patients who had been diagnosed with fulminant type 1 diabetes mellitus in China were analyzed retrospectively and then compared with those characteristics of 161 patients from a nationwide survey in Japan at the time of diagnosis and follow-up 6 months. RESULTS: The mean values of the characteristics from these two data sets, including fasting and postprandial serum C-peptide concentration, serum sodium and potassium level, positive for GADAb were significantly different (P=0.003, P=0.005, P=0.035, P=0.030, P<0.001, respectively). CONCLUSIONS: The clinical and biochemical characteristics of Chinese patients did not largely differ from those of Japanese patients. Further studies are needed for some unique characteristics found in our group.

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.

BACKGROUND: The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. METHODS: In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. RESULTS: The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, p<0.001), but no significant difference was found compared with the non-ketotic type 2 diabetics (0.73±0.19 mm, p=0.582) after controlling for differences in age and sex. In both the ketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both p<0.001) after controlling for sex, but no sex difference was observed (p=0.479 and p=0.707, respectively) after controlling for age. In the ketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. CONCLUSIONS: The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2 diabetics. The characteristics of carotid atherosclerotic lesions in the ketosis-onset diabetics resembled those in the non-ketotic type 2 diabetics. Our findings support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes.

Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review.

OBJECTIVE: To identify the factors associated with diabetic ketoacidosis at diagnosis of type 1 diabetes in children and young adults. DESIGN: Systematic review. DATA SOURCES: PubMed, EMBASE, Web of Science, Scopus, and Cinahl and article reference lists. STUDY SELECTION: Cohort studies including unselected groups of children and young adults presenting with new onset type 1 diabetes that distinguished between those who presented in diabetic ketoacidosis and those who did not and included a measurement of either pH or bicarbonate in the definition of diabetic ketoacidosis. There were no restrictions on language of publication. RESULTS: 46 studies involving more than 24,000 children in 31 countries were included. Together they compared 23 different factors. Factors associated with increased risk were younger age (for <2 years old v older, odds ratio 3.41 (95% confidence interval 2.54 to 4.59), for <5 years v older, odds ratio 1.59 (1.38 to 1.84)), diagnostic error (odds ratio 3.35 (2.35 to 4.79)), ethnic minority, lack of health insurance in the US (odds ratio 3.20 (2.03 to 5.04)), lower body mass index, preceding infection (odds ratio 3.14 (0.94 to 10.47)), and delayed treatment (odds ratio 1.74 (1.10 to 2.77)). Protective factors were having a first degree relative with type 1 diabetes at the time of diagnosis (odds ratio 0.33 (0.08 to 1.26)), higher parental education (odds ratios 0.4 (0.20 to 0.79) and 0.64 (0.43 to 0.94) in two studies), and higher background incidence of type 1 diabetes (correlation coefficient -0.715). The mean duration of symptoms was similar between children presenting with or without diabetic ketoacidosis (16.5 days (standard error 6.2) and 17.1 days (6.0) respectively), and up to 38.8% (285/735) of children who presented with diabetic ketoacidosis had been seen at least once by a doctor before diagnosis. CONCLUSIONS: Multiple factors affect the risk of developing diabetic ketoacidosis at the onset of type 1 diabetes in children and young adults, and there is potential time, scope, and opportunity to intervene between symptom onset and development of diabetic ketoacidosis for both parents and clinicians.

Fulminant type 1 diabetes mellitus-like presentation in a Hispanic woman in the United States.

AIM: To report the first case of fulminant-like type 1 diabetes mellitus in a Hispanic woman from the United States. METHOD: The clinical presentation and laboratory data is presented of a Hispanic woman that was diagnosed with fulminant type 1 diabetes mellitus with a review of the literature. RESULTS: An 18-year-old female presented with 1 week of polydyspea and polyuria. The patient was seen by her primary care doctor and found to have an elevated blood glucose. On presentation to the hospital, she was found to be in diabetic ketoacidosis. The laboratory analysis showed a C-peptide of 0.6 ng/mL and a glycohaemoglobin A(1c) of 6%. The patient had antibodies positive for glutamic acid decarboxylase. The patient was diagnosed with fulminant type 1 diabetes mellitus and was discharged in stable condition on basal/bolus subcutaneous insulin. CONCLUSION: Fulminant type 1 diabetes mellitus is a recently described presentation of diabetes mellitus that has been predominately reported in Japan and other Asian countries. The classical presentation includes rapid onset on ketosis within 1 week of symptoms of hyperglycaemia, with a near-normal glycohaemoglobin and absence of C-peptide. With the majority of case being reported from Asia, it has been hypothesized that there is a genetic determent that predisposes Asian individuals to develop fulminant type 1 diabetes mellitus. The addition of the case to the medical literature expands the focus of fulminant type 1 diabetes mellitus beyond the Asian population and supports the need that further research.

Japanese cases of acute onset diabetic ketosis without acidosis in the absence of glutamic acid decarboxylase autoantibody.

We report consecutive Japanese patients presented with acute onset diabetic ketosis who had negative glutamic acid decarboxylase autoantibody (GADAb) to clarify the clinical characteristics of them. A total of consecutive 1,296 in-patients with newly diagnosed diabetes mellitus, who were admitted to our center from April 2003 to October 2008, were analyzed. Among them, 17 patients who presented with acute onset diabetic ketosis without acidosis, and found to be negative for GADAb, were included. They showed male preponderance (n = 15). Ten patients had history of excessive ingestion of sugar-containing soft drink. Patients who successfully withdrew insulin therapy by 6 months (n = 7) showed significantly higher insulin secretion capacity and higher body mass index at the time of diagnosis than those who continued insulin therapy at least for 6 months (n = 10). These findings suggest that some of Japanese patients who presented with acute onset diabetic ketosis and negative for GADAb share several clinical characteristics with atypical type 2 diabetes such as ketosis-prone diabetes and "soft-drink ketosis," but others do not.

[PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes].

OBJECTIVE: To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population. METHODS: We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography(DHPLC) in 112 non-diabetes control subjects (NC group) and 141 patients with ketosis-prone diabetes (KPD group), who were both negative for glutamic acid decarboxylase antibody (GAD-Ab) as well as protein tyrosine phosphatase antibody (IA-2Ab). The sequences of abnormal peaks were analyzed by DNA-sequencing. The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 non-diabetic control subjects and 141 KPD patients. RESULTS: No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls. There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9, which induced missence mutation P321H (rs712701). No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects (P=0.532, 0.426). The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender (P=0.009,0.028). According to age at diagnosis, the difference was observed in the CC genotype and C allele frequencies between <20 years old and > or = 20 years old in the KPD group (P=0.034,0.032). The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group (P=0.005). CONCLUSION: A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population. However, A1168C variation may contribute to the predisposition to the male or < 20 years old patients with islet autoantibody-negative KPD.