c-peptide and Diabetic-Ketoacidosis

Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM) is a distinct form of autoimmune diabetes that is a rare complication of immune checkpoint inhibitor therapy. Data regarding CIADM are limited.. To systematically review available evidence to identify presentation characteristics and risk factors for early or severe presentations of adult patients with CIADM.. MEDLINE and PubMed databases were reviewed.. English full text articles from 2014 to April 2022 were identified with a predefined search strategy. Patients meeting diagnostic criteria for CIADM with evidence of hyperglycemia (blood glucose level >11 mmol/L or HbA1c ≥6.5%) and insulin deficiency (C-peptide <0.4 nmol/L and/or diabetic ketoacidosis [DKA]) were included for analysis.. With the search strategy we identified 1,206 articles. From 146 articles, 278 patients were labeled with "CIADM," with 192 patients meeting our diagnostic criteria and included in analysis.. Mean ± SD age was 63.4 ± 12.4 years. All but one patient (99.5%) had prior exposure to either anti-PD1 or anti-PD-L1 therapy. Of the 91 patients tested (47.3%), 59.3% had susceptibility haplotypes for type 1 diabetes (T1D). Median time to CIADM onset was 12 weeks (interquartile range 6-24). DKA occurred in 69.7%, and initial C-peptide was low in 91.6%. T1D autoantibodies were present in 40.4% (73 of 179) and were significantly associated with DKA (P = 0.0009) and earlier time to CIADM onset (P = 0.02).. Reporting of follow-up data, lipase, and HLA haplotyping was limited.. CIADM commonly presents in DKA. While T1D autoantibodies are only positive in 40.4%, they associate with earlier, more severe presentations.

Topics: Adult; Aged; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Insulin, Regular, Human; Middle Aged; Risk Factors

Postmortem chemistry is becoming increasingly essential in the forensic pathology routine and considerable progress has been made over the past years. Biochemical analyses of vitreous humor, cerebrospinal fluid, blood and urine may provide significant information in determining the cause of death or in elucidating forensic cases. Postmortem chemistry may essentially contribute in the determination of the cause of death when the pathophysiological changes involved in the death process cannot be detected by morphological methods (e.g. diabetes mellitus, alcoholic ketoacidosis and electrolytic disorders). It can also provide significant information and useful support in other forensic situations, including anaphylaxis, hypothermia, sepsis and hormonal disturbances. In this article, we present a review of the literature that covers this vast topic and we report the results of our observations. We have focused our attention on glucose metabolism, renal function and electrolytic disorders.

Topics: Biomarkers; Bodily Secretions; Body Fluids; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Electrolytes; Forensic Pathology; Fructosamine; Glucose; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Ketone Bodies; Kidney Function Tests; Postmortem Changes

Fulminant type 1 diabetes is defined as a subtype of type 1 diabetes with a remarkably acute onset. A nationwide survey identified that this variant accounts for approximately 20% of acute-onset type 1 diabetic patients in Japan. Recent studies indicate that this is not a minor subtype in other East Asian countries. As genetic factors, we revealed association of HLA-DR-DQ, HLA-B and CTLA-4 to fulminant type 1 diabetes. As an environmental factor, viral infection would contribute to the development of this subtype. Cellular infiltration to islets was detected soon after the onset but not observed 1 month after the onset. Macrophages and T cells were the main components of the infiltrates. Enterovirus RNA and Toll-like receptor-3 expression, a signature of viral infection, was also observed. These findings suggest that viral infection in the susceptible individual might trigger anti-viral immune response and that pancreatic beta cells are rapidly destroyed through the accelerated immune reaction.

Topics: Acute Disease; Adult; Aged; Asia, Eastern; Blood Glucose; C-Peptide; CTLA-4 Antigen; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Enterovirus Infections; Female; Glycated Hemoglobin; HLA-B Antigens; HLA-DRB1 Chains; Humans; Insulin-Secreting Cells; Japan; Male; Middle Aged; Virus Diseases

Topics: Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Early Diagnosis; Glycated Hemoglobin; HLA-DR4 Antigen; Humans; Insulin; Insulin-Secreting Cells; Japan; Linkage Disequilibrium; Prognosis; Th1 Cells; Time Factors; Virus Diseases

Type 1 diabetes mellitus is a multifactorial autoimmune disease characterized by destruction of insulin producing pancreatic beta cells that results in insulin deficiency and fasting hyperglycemia. It is now well known that the clinical onset of the disease represents the end stage of an immunological process that occurs over a course of months to years. During this period the presence of autoantibodies against different islet antigens can be detected by the use of standardized assays. The rate of beta cell loss is quite variable among different individuals and at onset ketoacidosis represents still a life threatening complication of the disease. The Diabetes Control and Complication Trial (DCCT) has clearly shown that the preservation of beta cell function in type 1 diabetic subjects results in a better metabolic control and significantly reduces the risk of microvascular complications. Consequently, markers of beta cell function represent important tools to make an early diagnosis and to evaluate the impact of new therapies on the natural history of the disease. The present review will focus on clinical markers currently available (intravenous glucose tolerance test, i.v.GTT, oral glucose tolerance test, OGTT, basal and stimulated C-peptide) to assess the beta cell function in type 1 diabetes.

Topics: Age Factors; Autoantibodies; Biomarkers; C-Peptide; Cell Death; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diabetic Retinopathy; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans

The availability of C-peptide measurement continues to provide new and useful information about the state of beta cell secretory function and the natural history of diabetes. Measurement of proinsulin is of value in the diagnosis of insulin-secreting tumors.

Topics: C-Peptide; Cross Reactions; Diabetes Mellitus; Diabetic Ketoacidosis; Humans; Immunoassay; Peptides; Proinsulin

Diabetic ketosis (DK) is one of the leading causes of hospitalization among patients with diabetes. Failure to recognize DK symptoms may lead to complications, such as diabetic ketoacidosis, severe neurological morbidity, and death.. This study aimed to develop and validate a model to predict DK in patients with type 2 diabetes mellitus (T2DM) based on both clinical and biochemical characteristics.. A cross-sectional study was conducted by evaluating the records of 3,126 patients with T2DM, with or without DK, at The Affiliated Hospital of Qingdao University from January 2015 to May 2022. The patients were divided randomly into the model development (70%) or validation (30%) cohorts. A risk prediction model was constructed using a stepwise logistic regression analysis to assess the risk of DK in the model development cohort. This model was then validated using a second cohort of patients.. The stepwise logistic regression analysis showed that the independent risk factors for DK in patients with T2DM were the 2-h postprandial C-peptide (2hCP) level, age, free fatty acids (FFA), and HbA1c. Based on these factors, we constructed a risk prediction model. The final risk prediction model was L= (0.472. This study identified independent risk factors for DK in patients with T2DM and constructed a prediction model based on these factors. The present findings provide an easy-to-use, easily interpretable, and accessible clinical tool for predicting DK in patients with T2DM.

Topics: C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans

To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis.. We enrolled 28 patients with type 1 diabetes, aged 14-30 years, in a prospective AHSCT phase II clinical trial. HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin. Changes in the exogenous insulin requirement were observed and serum levels of HbA(1c), C-peptide, and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT.. After transplantation, complete remission (CR), defined as insulin independence, was observed in 15 of 28 patients (53.6%) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months. The non-DKA patients achieved a greater CR rate than the DKA patients (70.6% in non-DKA vs. 27.3% in DKA, P = 0.051). In the non-DKA group, the levels of fasting C-peptide, peak value during oral glucose tolerance test (C(max)), and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up (all P < 0.05). In the DKA group, significant elevation of fasting C-peptide levels and C(max) levels was observed only at 18 and 6 months, respectively. There was no mortality.. We have performed AHSCT in 28 patients with type 1 diabetes. The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glucose Tolerance Test; Glutamate Decarboxylase; Hematopoietic Stem Cell Transplantation; Humans; Insulin; Male; Prospective Studies; Remission Induction; Transplantation, Autologous

The aim of this crossover trial was to evaluate the potential of partial substitution of basal insulin with glargine, administered once daily in the morning, to protect against nocturnal ketosis after postprandial interruption of continuous subcutaneous insulin infusion (CSII).. Seven patients with type 1 diabetes received 4 weeks of treatment with insulin lispro, administered by CSII, and 4 weeks of treatment with CSII and a partial basal replacement dose of insulin glargine administered in the morning. On day 28 of each treatment phase, patients were admitted to the research unit where dinner was served and their usual dinner insulin bolus dose given, after which CSII was discontinued at 7 pm. Plasma (p) beta-hydroxybutyrate and p glucose were measured every hour for 12 h thereafter.. Plasma beta-hydroxybutyrate at 7 pm was 0.16+/-0.05 and 0.13+/-0.07 mmol/l with and without glargine, respectively, and increased to 0.17+/-0.10 and 0.60+/-0.3 mmol/l within 6 h (P=0.02). Plasma glucose increased without glargine, from 8.6+/-2.9 to 21.1+/-3.0 mmol/l (P=0.003), but did not rise significantly following glargine (13.6+/-4.7 vs. 12.6+/-5.6 mmol/l; P=0.65).. Partial replacement with a morning dose of insulin glargine protects against the development of ketosis for as much as 12 h after postprandial interruption of CSII. This treatment strategy could, therefore, be useful for patients who are prone to ketosis but, for other reasons, are deemed suitable for CSII.

Topics: Adult; Blood Glucose; C-Peptide; Circadian Rhythm; Cross-Over Studies; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Infusion Systems; Insulin Lispro; Insulin, Long-Acting; Male; Middle Aged

Diabetic ketoacidosis is a serious complication of type diabetes. beta-Hydroxybutyrate (beta-OHB) accounts for about 75% of ketones, and blood concentration can be determined with a sensor. The aim of this study was to investigate the frequency and degree of ketonemia in daily life of children with diabetes and to make a base for recommendations for determination of ketonemia in clinical practice. During 3 months 45 patients with type 1 diabetes since 1-10 years old (mean 4.4 +/- 3.3 years old) at the pediatric clinic in Linköping, Sweden, performed 24-h profiles (eight determinations) in 2 weeks with blood glucose and beta-OHB. The children performed 11,189 blood glucose and 7,057 beta-OHB measurements. Only 0.3% (n = 21) of beta-OHB measurements were > or = 1.0 mmol/L. An beta-OHB concentration > 0.2 mmol/L was more common in the morning than during the rest of the day (p < 0.001). Young children (4-7 years old) had values > or = 0.2 mmol/L more often than adolescents (p < 0.001). Blood glucose values > 15 mmol/L were more often accompanied by beta-OHB > 0.2 mmol/L (p < 0.001). High beta-OHB concentrations are rare in diabetic children with reasonably good metabolic control. Already a value > 0.4 mmol/L seems abnormal, and we recommend that patients retest glucose and ketones with beta-OHB > 0.4 mmol/L. Furthermore, we recommend that diabetic children and adolescents measure beta-OHB when symptoms like nausea or vomiting occur to differentiate ketoacidosis from gastroenteritis, and during infections, during periods with high blood glucose (> 15 mmol/L), and if they notice ketonuria. Monitoring beta-OHB should be routine for patients on pump therapy.

Topics: 3-Hydroxybutyric Acid; Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Circadian Rhythm; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Infant; Insulin; Ketones; Male

When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers.. This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia.. The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups.. Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises.

Topics: Adult; Alleles; Autoantibodies; Black People; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Genotype; HLA-DQ Antigens; HLA-DR Antigens; Humans; Immunogenetics; Insulin; Insulin Secretion; Male; Obesity

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.

Topics: Adipose Tissue; Administration, Oral; Adult; Blood Glucose; C-Peptide; Carnitine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Fatty Acids; Fatty Acids, Nonesterified; Female; Glucagon; Glycerol; Humans; Hydroxybutyrates; Ketones; Liver; Male; Triglycerides

Many newly diagnosed obese African-American patients with history of severe hyperglycemia or diabetic ketoacidosis (DKA) are able to discontinue pharmacological treatment with continued good metabolic control. However, many of these individuals relapse into hyperglycemia within 1 year. In such patients, we compared the effect of low-dose sulfonylurea and dietary therapy in the prevention of recurrence of hyperglycemia.. We conducted an intention-to-treat study in 35 obese newly diagnosed diabetic patients (17 with DKA and 18 with severe hyperglycemia). After discontinuation of insulin, seven of 17 patients with DKA and seven of 18 patients with hyperglycemia were managed with diet and glyburide (1.25-2.5 mg/day), whereas other patients were followed with diet alone. In all patients, pancreatic insulin reserve was documented 1 day after resolution of hyperglycemic crises and within 1 week of discontinuation of insulin. Recurrence of hyperglycemia was defined as fasting blood glucose > 7.8 mmol/l (140 mg/dl) or random blood glucose > 10 mmol/l (180 mg/dl) on two or more consecutive determinations, or HbA1c > 7.5%.. Both treatment groups were comparable in age, sex, duration of diabetes, months of insulin therapy, BMI, glucose, and HbA1c. At presentation, the acute C-peptide response to glucagon in obese DKA patients was lower than in patients with hyperglycemia (P < 0.01), but responses were comparable after discontinuation of insulin. Sulfonylurea treatment significantly reduced recurrence of hyperglycemia in both obese DKA and obese hyperglycemic patients (P = 0.03). With a median follow-up of 16 months, hyperglycemia recurred in six of 10 DKA patients and in five of 11 hyperglycemia patients treated with diet alone, compared with one of seven DKA and one of seven hyperglycemia patients treated with glyburide. Readmission with metabolic decompensation occurred in four patients treated with diet but in none of the patients treated with diet and glyburide.. Low-dose sulfonylurea therapy prevents recurrence of hyperglycemia in newly diagnosed obese African-American patients with a history of hyperglycemic crises.

Topics: Adult; Black or African American; Black People; Blood Glucose; C-Peptide; Combined Modality Therapy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diet, Diabetic; Female; Georgia; Glyburide; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Islets of Langerhans; Male; Middle Aged; Obesity; Recurrence

Type 1 diabetes mellitus (T1DM) is a common chronic systemic disease that threatens the health of children worldwide. Diabetic ketoacidosis (DKA) is the most severe acute complication of diabetes and can lead to death. This study aimed to explore the epidemiological features, clinical manifestations, and risk factors for DKA in children and adolescents newly diagnosed with T1DM in the Department of Endocrinology of the Children's Hospital of Henan Province.. Medical records of 683 children and adolescents newly diagnosed with T1DM in our center from March 2014 to November 2021 were retrospectively analyzed. The data included the general condition, laboratory indexes, and clinical symptoms. The patients were divided into three groups according to age: Group I, 0-3 years; Group II, 4-9 years; and Group III, 10-18 years.. The incidence of DKA was 62.96% and was highest in Group I. Group I had the lowest C-peptide and hemoglobin A1c, but the highest blood glucose at first diagnosis, and 25-hydroxyvitamin D3 levels, hospitalization lengths, and medical costs. 25.5% of the children were delayed in diagnosis. Logistic regression analysis showed that elevated HbA1c levels and hyperglycemia were independent risk factors for DKA. On the other hand, C-peptide and 25- hydroxyvitamin D were protective factors for DKA.. The incidence of DKA among children and adolescents in the Henan Province is very high. Moreover, DKA can be easily delayed in diagnosis. Newly diagnosed infants with T1DM are more likely to present with DKA, suffer more severe metabolic disorders, endure longer hospital stays, and accrue higher medical costs.

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Hyperglycemia; Infant; Infant, Newborn; Retrospective Studies; Risk Factors

Therapeutic targets in type 2 diabetes mellitus (T2D) are oriented towards nephron- and cardio-protection and the prescription of antihyperglycemic agents with proven renal and cardiovascular benefits are increasing over time. Failure to promptly diagnose insulinopenic diabetes may adversely affect the adequacy of treatment and have harmful consequences, including severe hyperglycemia and diabetic ketoacidosis.. Deprescribing insulin therapy in T2D patients in favor of other antihyperglycemic medications has become a growing therapeutic opportunity to provide adequate glucose control, promote weight loss, improve insulin sensitivity, and ameliorate cardiovascular and renal outcomes. However, a blunted insulin reserve poses significant restriction on the prescription of non-insulin agents (e.g., diabetic ketoacidosis due to gliflozins). According to our experience, the routine testing of insulin reserve provides detailed information on diabetes pathophysiology with positive implications for the appropriateness of pharmacological prescriptions.. As part of our routine evaluation of diabetic patients, C-peptide measurement is a valuable and inexpensive tool to reclassify diabetes types and provide more appropriate disease management.

Topics: C-Peptide; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Humans; Hypoglycemic Agents; Insulin; Middle Aged

The destruction of pancreatic β cells causes type 1 diabetes mellitus (T1D), an autoimmune disease. Studies have demonstrated that there is heterogeneity in residual β-cell function in Caucasians; therefore, we aimed to evaluate β-cell function in Chinese autoimmune T1D patients.. β-cell function was determined using oral glucose tolerance testing or standardized steamed bread meal tolerance test in 446 participants with autoantibody-positive T1D. Clinical factors, such as age onset, sex, duration, body mass index, autoantibodies, other autoimmune diseases, diabetic ketoacidosis, hypoglycemia events, glycosylated hemoglobin, and insulin dose, were retrieved. We also analyzed single nucleotide polymorphism (SNP) data for C-peptides from 144 participants enrolled in the Chinese-T1D genome-wide association study.. Of 446 T1D patients, 98.5%, 97.4%, 86.9%, and 42.6% of individuals had detectable C-peptide values (≥ 0.003 nmol/L) at durations of < 1 year, 1 to 2 years, 3 to 6 years, and ≥ 7 years, respectively. A total of 60.7% of patients diagnosed at ≥ 18 years old and 15.8% of those diagnosed at < 18 years had detectable C-peptide after ≥ 7 years from the diagnosis. Furthermore, the patients diagnosed at ≥ 18 years old had higher absolute values of stimulated C-peptide (≥ 0.2 nmol/L). Diabetic ketoacidosis, hypoglycemia events, and insulin doses were shown to be associated with β-cell function. SNPs rs1770 and rs55904 were associated with C-peptide levels.. Our results have indicated that there are high residuals of β-cell mass in Chinese patients with autoimmune T1D. These findings may aid in the consideration of therapeutic strategies seeking prevention and reversal of β-cell function among Chinese T1D patients.

Topics: Adolescent; Autoantibodies; Autoimmune Diseases; C-Peptide; China; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Genome-Wide Association Study; Humans; Hypoglycemia; Insulin

The aim was to evaluate the impact of familial autoimmunity on the age and severity of type 1 diabetes (T1D) presentation and on the coexistence of other autoimmune diseases.. We retrospectively evaluated the medical records of 121 children/adolescents (male: 63) followed in our Diabetic Clinic from 2002 to 2016.. Seventy-six patients (62.8%) had at least one relative with an autoimmune disease, Hashimoto's thyroiditis (49.5%) and T1D (22.3%) being the commonest. Children with familial autoimmunity were younger at T1D diagnosis (mean age ± SD) (6.766 ± 3.75). Median fasting c-peptide levels at presentation were not related to familial autoimmunity. Patients with familial autoimmunity more often exhibited GADA autoantibody positivity at diagnosis. The larger the number of the patient's relatives diagnosed with an autoimmune disease, the higher were the patient's GADA levels (Spearman's rho test = 0.19, p = 0.049). Children with a first-degree relative with autoimmunity had a coexisting autoimmune disorder at a significantly higher percentage (p = 0.016). Family history of autoimmunity was negatively associated with the presence of diabetic ketoacidosis (DKA) (p = 0.024). Patients with a relative with T1D less frequently exhibited DKA at diagnosis (12.8 vs. 87.2%, p = 0.003). The presence of DKA was associated with younger age (p = 0.05) and lower c-peptide levels (p = 0.033).. Familial autoimmunity was present in 62.8% of children with T1D, autoimmune thyroiditis and T1D being the two most frequent familial autoimmune diseases. Familial autoimmunity reduced the risk of DKA at diagnosis, but these patients were younger and had higher levels of pancreatic autoantibodies and a greater risk of developing additional autoimmune diseases.

Topics: Autoantibodies; Autoimmune Diseases; Autoimmunity; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Hashimoto Disease; Humans; Male; Retrospective Studies

Objective This study analyzed the clinical and laboratory parameters that might influence the clinical outcomes of patients with type 2 diabetes who develop diabetic ketoacidosis (DKA), which has not been well investigated. Methods We reviewed the clinical and laboratory data of 158 patients who were hospitalized due to DKA between January 2006 and June 2019 and compared the data of patients stratified by the type of diabetes. In addition, the patients with type 2 diabetes were subdivided according to age, and their clinical and laboratory findings were evaluated. Results Patients with type 2 diabetes had a longer symptom duration associated with DKA, higher body mass index (BMI), and higher C-peptide levels than those with type 1 diabetes (p<0.05). Among patients with type 2 diabetes, elderly patients (≥65 years old) had a longer duration of diabetes, higher frequency of DKA onset under diabetes treatment, higher effective osmolarity, lower BMI, and lower urinary C-peptide levels than nonelderly patients (<65 years old) (p<0.05). A correlation analysis showed that age was significantly negatively correlated with the index of insulin secretory capacity. Conclusion Patients with DKA and type 2 diabetes had a higher BMI and insulin secretion capacity than those with type 1 diabetes. However, elderly patients with type 2 diabetes, unlike younger patients, were characterized by a lean body, impaired insulin secretion, and more frequent DKA development while undergoing treatment for diabetes.

Topics: Aged; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Insulin Secretion; Retrospective Studies

C-peptide is conventionally used in assessing pancreatic function in patients with diabetes mellitus. The clinical significance of this molecule during the course of type 1 diabetes mellitus (T1DM) has been recently revisited. This study aimed to investigate the natural course of C-peptide in T1DM patients over the period of 15 years and analyze the association between the residual C-peptide and diabetes complications.. This retrospective study included a total of 234 children and adolescents with T1DM. Patient data including sex, age at diagnosis, anthropometric measures, daily insulin dose, serum HbA1c, post-prandial serum C-peptide levels, lipid profiles, and diabetic complications at the time of diagnosis and 1, 3, 5, 10, and 15 years after diagnosis were retrospectively collected.. Among the 234 patients, 101 were men and 133 were women, and the mean patient age at initial diagnosis was 8.3 years. Serum C-peptide decreased constantly since the initial diagnosis, and showed a significant decline at 3 years after diagnosis. At 15 years after diagnosis, only 26.2% of patients had detectable serum C-peptide levels. The subgroup with older patients and patients with higher BMI standard deviation score showed higher mean serum C-peptide, but the group-by-time results were not significant, respectively. Patients with higher serum C-peptide required lower doses of insulin and had fewer events of diabetic ketoacidosis.. Serum C-peptide decreased consistently since diagnosis of T1DM, showing a significant decline after 3 years. Patients with residual C-peptide required a lower dose of insulin and had a lower risk for diabetic ketoacidosis.

Topics: Adolescent; C-Peptide; Child; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Female; Humans; Insulin; Male; Retrospective Studies

Insulin antibodies (IAs) induced by exogenous insulin rarely cause hypoglycemia. However, insulin autoantibodies (IAAs) in insulin autoimmune syndrome (IAS) can cause hypoglycemia. The typical manifestations of IAS are fasting or postprandial hypoglycemia, elevated insulin level, decreased C-peptide levels, and positive IAA. We report a 45-year-old male with type 1 diabetes mellitus (T1DM) treated with insulin analogues suffering from recurrent hypoglycemic coma and diabetic ketoacidosis (DKA). His symptoms were caused by exogenous insulin and were similar to IAS. A possible reason was that exogenous insulin induced IA. IA titers were 61.95% (normal: < 5%), and the concentrations of insulin and C-peptide were > 300 mU/L and < 0.02 nmol/L when hypoglycemia occurred. Based on his clinical symptoms and other examinations, he was diagnosed with hyperinsulinemic hypoglycemia caused by IA. His symptoms improved after changing insulin regimens from insulin lispro plus insulin detemir to recombinant human insulin (Gensulin R) and starting prednisone.

Topics: Autoimmune Diseases; C-Peptide; Coma; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Antibodies; Male; Middle Aged

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they may cause immune-related adverse events. Although there have been a few reports of new-onset type 1 diabetes mellitus (T1DM) during ICI treatment, T1DM as a delayed immune-related event after discontinuing immunotherapy is extremely rare. Herein, we report the case of an elderly veteran who presented with diabetic ketoacidosis 4 months after the discontinuation of treatment with nivolumab.. A 74-year-old veteran was treated with second-line nivolumab for advanced non-small cell lung cancer. After 9 treatment cycles, the administration was discontinued due to fatigue. Four months later, he was admitted to the emergency department in a stuporous mental state and hyperglycemia, with high glycosylated hemoglobin levels (10.6%). C-peptide levels were significantly decreased, with negative islet autoantibodies.. We diagnosed nivolumab-induced T1DM. There were no laboratory results indicating a new thyroid dysfunction or adrenal insufficiency, which are typical endocrine adverse reactions.. Since the hypothalamic and pituitary functions were preserved and only the pancreatic endocrine capacity was impaired, we administered continuous intravenous insulin injections, with fluid and electrolyte replacement.. His serum glucose levels decreased, and symptoms improved; hence, on the 8 day of hospitalization, we switched to multiple daily insulin injections.. The present case indicates that regular glucose monitoring and patient education are needed for diabetic ketoacidosis after the discontinuation of ICI therapy.

Topics: Aged; Autoantibodies; Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Carcinoma, Non-Small-Cell Lung; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Electrolytes; Glycated Hemoglobin; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Male; Nivolumab

Fulminant type 1 diabetes mellitus (FT1DM) is recognised as a novel subtype of type 1 diabetes mellitus characterised by the abrupt onset of insulin-deficient hyperglycaemia and ketoacidosis. Fulminant type 1 diabetes mellitus is known to be associated with pregnancy and had been associated with high fetal mortality. We report a case of a gestational diabetes mellitus (GDM) mother complicated with FT1DM immediately post-delivery. A 29-year-old Malay lady who was diagnosed with GDM at 19 weeks of pregnancy, underwent emergency lower segment caesarean section (EMLSCS) due to fetal distress at 36 weeks of gestation; 18 h post-EMLSCS, she developed abrupt onset Diabetic ketoacidosis (DKA) (blood glucose 33.5 mmol/L, pH 6.99, bicarbonate 3.6 mmol/L, ketone 4.4 mmol/L and HbA1c 6.1%). She received standard DKA treatment and discharged well. Her plasma C-peptide level 3 weeks later showed that she has no insulin reserve (C-peptide <33 pmol/L, fasting blood glucose (FBS) 28 mmol/L). Her pancreatic autoantibodies were negative. This case highlights that FT1DM not only can occur in pregnancy with normal glucose tolerance but can also complicate mother with GDM.

Topics: Adult; Autoantibodies; Bicarbonates; Blood Glucose; C-Peptide; Cesarean Section; Diabetes Mellitus, Type 1; Diabetes, Gestational; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Insulin; Ketones; Mothers; Pregnancy

We aimed to determine the hospital-based prevalence and clinical features of fulminant type 1 diabetes mellitus in Korea.. We identified all patients with diabetes who regularly visited the Endocrinology outpatient clinics at eight centers for a period >1 year between January 2012 and June 2017. We investigated their medical records retrospectively.. During this period, 76,309 patients with diabetes had been regularly followed up. Among them, 913 (1.2%) patients had type 1 diabetes mellitus . There were 462 patients with type 1 diabetes mellitus whose data at the time of the first diagnosis could be identified (359 and 103 with non-ketosis and ketosis onset, respectively). Of these, 15 (3.2% of type 1 diabetes mellitus, 14.6% of ketosis onset diabetes) patients had fulminant type 1 diabetes mellitus. The median ages at diagnosis were 40 and 27 years in the fulminant type 1 diabetes mellitus and non-fulminant type 1 diabetes mellitus groups, respectively. The patients with fulminant type 1 diabetes mellitus had higher body mass index, lower glycated hemoglobin and fasting/peak C-peptide, and lower frequent glutamic acid decarboxylase antibody-positive rate (P =0.0010) at diagnosis. Furthermore, they had lower glycated hemoglobin at the last follow-up examination than those with non-fulminant type 1 diabetes mellitus.. In this study, the prevalence of type 1 diabetes mellitus was 1.2% among all patients with diabetes, and that of fulminant type 1 diabetes mellitus was 3.2% among those newly diagnosed with type 1 diabetes mellitus. The glycated hemoglobin levels were lower in patients with fulminant type 1 diabetes mellitus than in those with non-fulminant type 1 diabetes mellitus at diagnosis and at the last follow-up examination.

Topics: Adult; Asian People; Autoantibodies; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Male; Middle Aged; Prevalence; Republic of Korea; Retrospective Studies

A positive relationship between the recently emerged Corona Virus Disease-19 (COVID-19) and diabetes has been inferred, but not confirmed, in children. The aim of the present study was to investigate the possible impact of COVID-19 on new-onset Type-1 Diabetes Mellitus (T1DM) in a pediatric population.. This is a prospective study of all children and adolescents diagnosed with T1DM during the first year of the COVID-19 pandemic (March 2020-February 2021) in Western Greece (population coverage ≈1,000,000). The incidence and severity of T1DM, the age and sex of the participants and HbA1c and c-peptide concentrations at diagnosis were recorded and compared to those of the previous year (pre-COVID-19 year).. 21 children aged 8.03±0.90 years old were diagnosed with T1DM in the COVID-19 year and 17, aged 9.44±3.72 years old, in the pre-COVID-19 year. A different seasonality pattern of new onsets was observed during the COVID-19 year compared to the previous year, with increasing trend from spring to winter (spring: 9.5% vs. 23.5%, autumn: 23.8% vs. 29.4%, summer: 19% vs. 11.8%, winter: 47.6% vs. 35.3%). Also, compared to the preceding year, HbA1c was significantly higher (p=0.012) and the incidence and severity of diabetic ketoacidosis greater (p=0.045, p=0.013, respectively).. This is the first study to report a different seasonality pattern and increased severity of new-onset T1DM during the first year of the COVID-19 pandemic. Future research should further investigate the possible role of SARS-CoV-2 and the different pattern of overall infection incidence during the COVID-19 year.

Topics: Adolescent; C-Peptide; Child; Child, Preschool; COVID-19; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Greece; Humans; Incidence; Male; Prospective Studies; Seasons

To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents.. Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D.. Mean ± SD age at diagnosis was 10.1 ± 4.3 years (range 0.7-17.6 years) with mode at 9-12 years. A female preponderance was observed. Fifty-two individuals (55.3%) presented in diabetic ketoacidosis (DKA). Mean ± SD serum fasting C-peptide values were 0.22 ± 0.25 nmol/L (0.66±0.74 ng/ml). 31.3% were autoantibody negative, 53.4% were GADA positive, 27.2% were IA-2A positive, with 12.1% positive for both autoantibodies. Association analysis compared to 198 controls of similar ethnic origin revealed strong locus association with HLA-DRB1 (p < 2.4 × 10. Young Sudanese individuals with T1D generally have similar characteristics to reported European-origin T1D populations. However, they have higher rates of DKA and slightly lower autoantibody rates than reported European-origin populations, and a particularly strong association with HLA-DRB1*03:01.

Topics: Adolescent; Age of Onset; Autoantibodies; Biomarkers; C-Peptide; Case-Control Studies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Genetic Predisposition to Disease; Genotype; Glutamate Decarboxylase; HLA-DRB1 Chains; Humans; Infant; Male; Sudan

The aim of this study was to observe the clinical features of type 2 diabetes mellitus (T2DM) patients with ketosis as the initial symptom, and investigate its differences from clinical features of non-ketotic T2DM patients.. A total of 385 T2DM patients treated in our hospital from 2014 to 2017 were selected and divided into ketosis-prone T2DM group and non-ketotic T2DM group. Ketosis-prone T2DM patients refer to DM patients with the urine ketone body++ or above or the blood ketone body ≥1.0 mmol/L when treated. Fasting venous blood was collected from all patients in the early morning at 2 d after admission to detect the liver function, renal function, blood glucose, triglyceride, total cholesterol, glycosylated hemoglobin and fasting C-peptide, glutamic acid decarboxylase antibody (GAD-Ab) and islet cell antibody (ICA) were also detected, and the 24 h urine specimen was retained to detect the 24 h urine microalbumin excretion rate.. The proportion of male in ketosis-prone T2DM group was significantly higher than that in non-ketotic T2DM group (P<0.01). Patients in ketosis-prone T2DM group was younger than those in non-ketotic T2DM group (P<0.05). The number of days from initial symptom to treatment in ketosis-prone T2DM group was smaller than that in non-ketotic T2DM group (P<0.05). The fasting C-peptide level in ketosis-prone T2DM group was significantly lower than that in non-ketotic T2DM group (P<0.05). The degree of weight loss and level of glycosylated hemoglobin in ketosis-prone T2DM group were significantly higher than those in non-ketotic T2DM group (P<0.05).. Ketosis-prone T2DM patients are characterized by lower age at onset, higher proportion of male, shorter duration of disease, poorer islet function, higher blood glucose and more significant weight loss than non-ketotic T2DM patients.

Topics: Adult; Age Factors; Autoantibodies; Body Mass Index; C-Peptide; C-Reactive Protein; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Disease Susceptibility; Female; Glycated Hemoglobin; Humans; Ketosis; Lipids; Male; Middle Aged; Risk Factors; Sex Factors; Weight Loss

Objectives We aimed to evaluate children with type 1 diabetes (T1D) with early age at onset (EAO) for clinical, immune and metabolic features in order to identify age-related disease phenotypes. Methods Comparative study of two groups of T1D children: EAO (≤5 years) and later age at onset (LAO; >5 years), regarding the presence of other autoimmune (AI) diseases, diabetes ketoacidosis and immunologic profile at onset and metabolic data 1 year after diagnosis. Statistical analysis was performed with significance set for p < 0.05. Results The study included 137 children (EAO = 52, mean age 3.6 ± 1.5 [mean ± standard deviation (SD)] and LAO = 85, mean age 10.4 ± 2.9). EAO was more associated with concomitant AI diseases (p = 0.032). Despite no differences in disease onset, EAO presented with lower C-peptide levels (p = 0.01) and higher absolute lymphocyte number (p < 0.0001), with an inverse correlation between these two variables (p = 0.028). Additionally, the EAO group had a higher frequency of serum detection of three antibodies (Abs) (p = 0.0008), specifically insulin Abs (p = 0.0001). One year after diagnosis, EAO had higher total daily insulin (TDI) dose (p = 0.008), despite similar hemoglobin A1c (HbA1c). Conclusions Our data show an association of EAO T1D with more AI diseases, higher number of Abs, lower initial insulin reservoir and higher insulin requirements 1 year after diagnosis. In this group, immune imbalance seems more evident and disease progression faster, probably reflecting distinct "immune environment" with different ages at disease onset. Further studies in the field of immunogenetics and immune tolerance are required, to improve patient stratification and find novel targets for therapeutic intervention.

Topics: Adolescent; Age of Onset; Autoantibodies; Autoimmune Diseases; Biomarkers; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant; Infant, Newborn; Insulin; Male; Phenotype; Prognosis; Retrospective Studies

Cases of type 1 diabetes mellitus in children aged younger than 6 years in Taiwan has increased in the past 10 years. This retrospective study aimed to review the management experience of such patients in a single center.. From January 2004 to June 2015, 52 newly diagnosed diabetic children younger than 6 years who had regular follow-up for > 1 year were enrolled, as well as 94 older diabetic children for comparison. Their medical records were thoroughly reviewed.. The most common symptoms and signs were polyuria, polydipsia, dry lips, weight loss, and nocturia. Among the children younger than 6 years, 87% had ketoacidosis upon diagnosis-significantly higher than that of the older age group-and 88% had at least one islet cell autoantibody detected. Their serum C-peptide levels were significantly lower and the frequency of insulin autoantibodies detected was significantly higher compared with the older age group (37% vs. 10%). The remission rate of the young diabetic patients was significantly lower than that of the older age group (40% vs. 59%), but there was no difference in time of onset and duration of remission between the two groups.. Autoimmune destruction of pancreatic β-cells is an important cause of type 1 diabetes mellitus in Taiwanese children aged younger than 6 years. These patients usually have a low insulin reserve and severe ketoacidosis upon diagnosis. A high index of suspicion in the presence of classic symptoms of diabetes in young children is important to prevent complications.

Topics: Adolescent; Age Factors; Autoantibodies; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Lip; Male; Nocturia; Polydipsia; Polyuria; Symptom Assessment; Taiwan; Weight Loss

The aim of this study was to identify the risk factors for presence and severity of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in Korean children and adolescents. A retrospective chart review of children and adolescents newly diagnosed with T1DM was conducted in seven secondary and tertiary centers in Korea. Eligible subjects were < 20 years of age and had records on the presence or absence of DKA at the time of T1DM diagnosis. DKA severity was categorized as mild, moderate, or severe. Data were collected on age, height, body weight, pubertal status, family history of diabetes, delayed diagnosis, preceding infections, health insurance status, and parental education level. A total of 361 patients (male 46.3%) with T1DM were included. Overall, 177 (49.0%) patients presented with DKA at T1DM diagnosis. Risk factors predicting DKA at T1DM diagnosis were age ≥ 12 years, lower serum C-peptide levels, presence of a preceding infection, and delayed diagnosis. Low parental education level and preceding infection increased the severity of DKA. These results suggest that alertness of the physician and public awareness of diabetes symptoms are needed to decrease the incidence and severity of DKA at T1DM diagnosis.

Topics: Adolescent; Asian People; Body Weight; C-Peptide; Child; Child, Preschool; Delayed Diagnosis; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Male; Republic of Korea; Retrospective Studies; Risk Factors; Severity of Illness Index; Tertiary Care Centers

Fulminant type 1 diabetes is characterized by remarkably rapid and complete β-cell destruction. The established diagnostic criteria include the occurrence of diabetic ketosis soon after the onset of hyperglycemic symptoms, elevated plasma glucose with relatively low HbA1c at the first visit, and extremely low C-peptide. Serum C-peptide levels remain extremely low over a prolonged period. A 26-year-old-man with diabetic ketosis was admitted to our hospital. His relatively low HbA1c (7.6%), despite marked hyperglycemia (593 mg/dL) with marked ketosis, indicated abrupt onset. Islet-related autoantibodies were all negative. His data at onset, including extremely low serum C-peptide (0.11 ng/mL), fulfilled the diagnostic criteria for fulminant type 1 diabetes. However, his fasting serum C-peptide levels subsequently showed substantial recovery. While fasting C-peptide stayed below 0.30 ng/mL during the first two months post onset, the levels gradually increased and thereafter fluctuated between 0.60 ng/mL and 0.90 ng/mL until 24 months post onset. By means of multiple daily insulin injection therapy, his glycemic control has been well maintained (HbA1c approximately 6.0%), with relatively small glycemic fluctuations evaluated by continuous glucose monitoring. This clinical course suggests that, despite the abrupt diabetes onset with extremely low C-peptide levels, substantial numbers of β-cells had been spared destruction and their function later showed gradual recovery. Diabetes has come to be considered a much more heterogeneous disease than the present subdivisions suggest. This case does not fit into the existing concepts of either fulminant type 1 or ketosis-prone diabetes, thereby further highlighting the heterogeneity of idiopathic type 1 diabetes.

Topics: Adult; Blood Glucose; C-Peptide; Combined Modality Therapy; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Japan; Male; Severity of Illness Index; Treatment Outcome

To investigate the prevalence and clinical characteristics of ketosis-prone type 2 diabetes (KPD) in Chinese patients with young-onset diabetes.. A total of 238 young diabetic patients were recruited from our inpatient department from January 1, 2012, to December 28, 2014. KPD was defined as diabetes without precipitating illness and with the presence of ketosis or diabetic ketoacidosis in the absence of autoantibodies at the time of diagnosis. We reviewed the clinical characteristics and disease progression of this group of patients.. Eighteen patients fulfilled the criteria for KPD, and the prevalence of patients with KPD was 7.6%. The mean (SD) age of the KPD group at the time of diagnosis of diabetes was 27.6 (4.85) years, and these patients were predominantly male (male to female ratio, 8:1) and had a high proportion of obesity and new-onset diabetes and a strong family history of diabetes. β-Cell function in the KPD group was intermediate between type 1 and type 2 diabetes. Patients with KPD had the highest levels of glycated hemoglobin, triglycerides, total cholesterol, and free fatty acids and the lowest levels of high-density lipoprotein. After 3 to 12 months of follow-up, 17 of 18 patients with KPD (94.4%) were able to discontinue insulin therapy, and 11 patients (61.1%) were managed with diet or exercise alone.. KPD patients accounted for 7.6% of the diabetic patients requiring admission to a large urban hospital in China, with an age of onset of diabetes of ≤35 years. These patients are more likely to be male, have abnormal lipid metabolism, and have more reversible β-cell dysfunction.

Topics: Adolescent; Adult; Age of Onset; C-Peptide; China; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Humans; Male; Retrospective Studies; Young Adult

Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P = 0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC(0-0.5), AUC₀₋₁, AUC₀₋₃ (P < 0.05). Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P < 0.05). From these data, we concluded that ketosis onset T2DM had better islet β-cell function and more serious insulin resistance than nonketotic onset T2DM.

Topics: Adolescent; Adult; Aged; C-Peptide; Case-Control Studies; China; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fatty Liver; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Ketone Bodies; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Prevalence; Retrospective Studies; Young Adult

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.. Prospective cross sectional study.. Nelson Mandela Academic Hospital, Mthatha, Eastern Cape Province, South Africa.. Indigenous Black South Africans with ketoacidosis as the initial manifestation of diabetes.. 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.. 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.. 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.. 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.

Topics: Acanthosis Nigricans; Adolescent; Adult; Aged; Autoantibodies; Black People; C-Peptide; Cross-Sectional Studies; Diabetic Ketoacidosis; Female; Glutamate Decarboxylase; Humans; Insulin-Secreting Cells; Islets of Langerhans; Male; Middle Aged; Prospective Studies; Seroepidemiologic Studies; South Africa; Young Adult

This study was done to characterize the natural course of C-peptide levels in patients with type 1 diabetes and identify distinguishing characters among patients with lower rates of C-peptide decline. A sample of 95 children with type 1 diabetes was analyzed to retrospectively track serum levels of C-peptide, HbA1c, weight, BMI, and diabetic complications for the 15 yr after diagnosis. The clinical characteristics were compared between the patients with low and high C-peptide levels, respectively. The average C-peptide level among all patients was significantly reduced five years after diagnosis (P < 0.001). The incidence of diabetic ketoacidosis was significantly lower among the patients with high levels of C-peptide (P = 0.038). The body weight and BMI standard deviation scores (SDS) 15 yr after diagnosis were significantly higher among the patients with low C-peptide levels (weight SDS, P = 0.012; BMI SDS, P = 0.044). In conclusion, C-peptide level was significantly decreased after 5 yr from diagnosis. Type 1 diabetes patients whose beta-cell functions were preserved might have low incidence of diabetic ketoacidosis. The declines of C-peptide level after diagnosis in type 1 diabetes may be associated with changes of body weight and BMI.

Topics: Adolescent; Body Mass Index; Body Weight; C-Peptide; Child; Child, Preschool; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diabetic Retinopathy; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Incidence; Infant; Male; Peripheral Nervous System Diseases; Retrospective Studies

Type-1-diabetes mellitus (T1DM) is the most commonly diagnosed type of DM in children and adolescents. We aim to identify the epidemiological profile, risk factors, clinical features, and factors related to delayed diagnosis or mismanagement in children with newly diagnosed T1DM in Taif, Saudi Arabia.. Ninety-nine newly diagnosed patients were included in the study along with 110 healthy controls. Patients were classified into 3 groups (I: >2 years, II: 2->6 years, and III: 6-12 years). Both patients and controls were tested for C-peptide, TSH, and autoantibodies associated with DM and those attacking the thyroid gland.. Diabetic ketoacidosis was present in 79.8%. Delayed and missed diagnoses were recorded in 45.5%, with significant correlation to age and district of origin. Severity at presentation showed significant correlation with age and cow's milk feeding. Group I, those with misdiagnosis or positive DM related autoantibodies, had more severe presentations. The correlation of C-peptide and TSH levels in patients and controls was significant for C-peptide and nonsignificant for TSH.. Misdiagnosis and mismanagement are common and account for more severe presentation, especially in young children >2 years. Early introduction of cow's milk appears to be a risk factor for the development of T1DM.

Topics: Animals; C-Peptide; Child; Child, Preschool; Delayed Diagnosis; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Infant; Male; Milk; Risk Factors; Saudi Arabia; Thyrotropin

Ketosis-prone atypical diabetes (KPD) is a subtype of diabetes in which the pathophysiology is yet to be unraveled. The aim of this study was to characterize β- and α-cell functions in Africans with KPD during remission.. We characterized β- and α-cell functions in Africans with KPD during remission. The cohort comprised 15 sub-Saharan Africans who had been insulin-free for a median of 6 months. Patients in remission were in good glycemic control (near-normoglycemic) and compared with 15 nondiabetic control subjects matched for age, sex, ethnicity, and BMI. Plasma insulin, C-peptide, and glucagon concentrations were measured in response to oral and intravenous glucose and to combined intravenous arginine and glucose. Early insulin secretion was measured during a 75-g oral glucose tolerance test. Insulin secretion rate and glucagon were assessed in response to intravenous glucose ramping.. Early insulin secretion and maximal insulin secretion rate were lower in patients compared with control participants. In response to combined arginine and glucose stimulation, maximal insulin response was reduced. Glucagon suppression was also decreased in response to oral and intravenous glucose but not in response to arginine and insulin.. Patients with KPD in protracted near-normoglycemic remission have impaired insulin response to oral and intravenous glucose and to arginine, as well as impaired glucagon suppression. Our results suggest that β- and α-cell dysfunctions both contribute to the pathophysiology of KPD.

Topics: Adult; Black People; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glucagon; Glucagon-Secreting Cells; Glucose Tolerance Test; Humans; Insulin; Insulin-Secreting Cells; Male; Middle Aged

Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (< 69 mmol/mol, 8.5%), (3) rapid progression to diabetic ketoacidosis, (4) very low C-peptide level, and (5) often associated with elevated serum pancreatic enzymes, and absence of diabetes-related autoantibodies. We encountered a case of fulminant Type 1 diabetes that developed with an initial manifestation of the insulin autoimmune syndrome and rapidly progressed to diabetic ketoacidosis during pregnancy. A 31-year-old Korean woman presented with recurrent sudden onset of sweating and change of consciousness during sleep at 19 weeks gestation. During a 72-h fasting test, hypoglycaemia (1.72 mmol/l) occurred at 4 h after the start of the test. At that time, there was a high insulin level (370.2 μU/ml), a paradoxically low C-peptide level (0.01 nmol/l) and a positive insulin autoantibody test. An oral glucose tolerance test revealed postprandial hyperglycaemia. She was initially diagnosed as the insulin autoimmune syndrome. On the day 5 of admission, she developed diabetic ketoacidosis. Her HbA(1c) was 62 mmol/mol (7.8%). The rapid progression of diabetic ketoacidosis altered the diagnosis to fulminant Type 1 diabetes. This case differed from typical fulminant Type 1 diabetes because it presented with hypoglycaemia, and positive insulin and anti-phospholipid antibody tests. Her HLA typing was HLA-DQA1*0302, 0501, HLA-DRB1*0301 (DR3), 0901(DR9). Her glucose level was subsequently very well controlled with multiple insulin injections and she successfully delivered a healthy baby.

Topics: Adult; Antibodies, Antiphospholipid; Autoantibodies; Autoimmune Diseases; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Female; Glucose Tolerance Test; Glycated Hemoglobin; HLA-DQ alpha-Chains; HLA-DRB1 Chains; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Pregnancy; Pregnancy in Diabetics; Pregnancy Outcome; Syndrome

In continuation to part I, a literature review is presented concerning biochemical problems of forensic post mortem cases of unclear hyperglycaemia or hypoglycaemia. Clinical parameters for this purpose were recently reviewed. Particular attention was paid to the detection of diabetic ketoacidosis, of hyperosmolar coma, insulinoma, insulin-induced or oral diabetic-induced hypoglycaemia. The second part of the review discusses the analytes ketone bodies, synthetic insulins, human insulin, C-peptide, proinsulin and insulin antibodies. Special interest is given to post mortem matrices for those analytes to reference concentrations, stability data, analytic interferences and analytical procedures which should be used in toxicological laboratories willing to detect diabetic metabolism disorders after death.

Topics: C-Peptide; Diabetic Ketoacidosis; Drug Overdose; Forensic Pathology; Glucose Metabolism Disorders; Humans; Insulin; Ketone Bodies; Postmortem Changes; Proinsulin

Diabetic ketoacidosis (DKA) is still a severe complication associated with significant morbidity and mortality. The aim of this study was to determine the predictors of DKA in children with newly diagnosed type 1 diabetes mellitus (T1DM).. The study group consisted of new-onset type 1 diabetic patients admitted to our hospital between January 2006 and March 2008. One hundred and eighty-seven children were identified (95 females and 92 males) and their mean age was 8.9 ± 4.6 yr (0.8-17.8). Hemoglobin A1c, blood gases, and fasting c-peptide level were evaluated in all children. DKA was defined as a capillary pH < 7.3 and blood glucose >11 mmol/L.. At the time of T1DM diagnosis, 26% of children had DKA. Misdiagnosis was significantly associated with the incidence of DKA. In the group with DKA, c-peptide level was significantly lower than in the group without DKA (p = 0.003.) The most prone to DKA were children under 2 yr of age (n = 14). In this age group, DKA was present in 71% of individuals and the lowest c-peptide level was observed compared to older children (p < 0.0001). There was significant correlation between the c-peptide level and age of children (r = 0.41, p < 0.0001).. The incidence of DKA among newly diagnosed patients with T1DM remains unacceptably high and indicates greater necessity of medical alertness for this diagnosis, especially in the youngest children. Children under 2 yr of age remain the most prone to DKA, which may be related to delay in diagnosis and more aggressive β-cell destruction.

Topics: Adolescent; Aging; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diagnostic Errors; Female; Glycated Hemoglobin; Humans; Infant; Male; Poland; Risk Factors

The protein tyrosine phosphatase nonreceptor type 2 (PTPN22) has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c), glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA) and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab) in children during the first year after diagnosis of type 1 diabetes.. The C1858T variant was genotyped in an international cohort of children (n = 257 patients) with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association of this variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide) and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset.. A repeated measurement model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03) for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002), which did not influence the association between PTPN22 and proinsulin (est.: 1.28, p = 0.03).. The T allele of the C1858T variant is positively associated with proinsulin levels during the first 12 months in newly diagnosed type 1 diabetes children.

Topics: Autoantibodies; C-Peptide; Child; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Enzyme-Linked Immunosorbent Assay; Female; Genetic Predisposition to Disease; Humans; Male; Polymorphism, Single Nucleotide; Proinsulin; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Regression Analysis; Time Factors

Topics: Adolescent; C-Peptide; Dehydration; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Hypertension; Infant; Insulin; Patient Compliance

We investigated the effects of clinical and laboratory properties at the time of the initial application of patients recently diagnosed and presenting metabolic indicators of diabetic ketoacidosis who were given disease prognoses in years 1 and 2 after discharge.. A total of 94 patients admitted to Bakirkoy Maternity and Children's Diseases Training and Research Hospital with diabetic ketoacidosis and recently diagnosed with type 1 diabetes mellitus were investigated. Patient files were examined within 2 years following discharge.. All 94 study patients (53.2% male and 46.8% female) presented acidosis, ketonuria and hyperglycemia. While a moderate correlation was detected between the prodromal period and HbA(1c) values in year 1, only a slight correlation was seen in HbA(1c) values in year 2. In addition, a slight correlation was observed between the prodromal period and the number of hospitalizations due to diabetic ketoacidosis in the first year. Again, while a moderate correlation was observed between HbA(1c) values and the number of hospitalizations due to diabetic ketoacidosis in year 1, only a slight correlation was seen in year 2. The prodromal period was directly proportional to patient age.. Hospital admissions may be reduced through appropriate treatment, follow-up and metabolic control of patients with type 1 diabetes mellitus. In addition, we report a relationship between the prodromal period and HbA(1c) values in type 1 diabetes patients.

Topics: Blood Glucose; C-Peptide; Child; Child, Hospitalized; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Female; Glycated Hemoglobin; Humans; Incidence; Insulin; Male; Patient Readmission

To identify predictors of residual beta-cell function and glycemic control during the first 12 months after the diagnosis of type 1 diabetes (T1D).. Clinical information and blood samples were collected from 275 children. HbA1c, antibodies, HLA typing and mixed meal-stimulated C-peptide levels 1, 6, and 12 months after diagnosis were analyzed centrally.. Mean age at diagnosis was 9.1 yr. DKA with standard bicarbonate <15 mmol/L was associated with significantly poorer residual beta-cell function 1 (p = 0.004) and 12 months (p = 0.0003) after diagnosis. At 12 months, the decline in stimulated C-peptide levels compared with the levels at 1 month was 69% in the youngest age group and 50% in patients 10 yr and above (p < 0.001). Stimulated C-peptide at 12 months was predicted by younger age (p < 0.02) and bicarbonate levels at diagnosis (p = 0.005), and by stimulated C-peptide (p < 0.0001), postmeal blood glucose (p = 0.0004), insulin antibodies (IA; p = 0.02) and glutamic acid decarboxylase antibodies (GADA; p = 0.0004) at 1 month. HbA1c at 12 months was predicted by HbA1c at diagnosis (p < 0.0001), GADA at 1 month (p = 0.01), and non-white Caucasian ethnicity (p = 0.002).. Younger age, ketoacidosis at diagnosis, and IA and GADA 1 month after diagnosis were the strongest explanatory factors for residual beta-cell function at 12 months. Glycemic control at 12 months was influenced predominantly by ethnicity, HbA1c at diagnosis, and GADA at 1 month.

Topics: Adolescent; Autoantibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glutamate Decarboxylase; Glycated Hemoglobin; HLA Antigens; Humans; Hypoglycemic Agents; Infant; Insulin; Insulin Antibodies; Insulin-Secreting Cells; Male; Multicenter Studies as Topic; Prospective Studies; Treatment Outcome

In type 1 diabetic patients, some have glycemic instability while others glycemic stability. We have developed criteria for evaluating glycemic instability and investigated the factors responsible.. Glycemic instability in 52 type 1 diabetic patients was assessed by the mean amplitude of glycemic excursions (MAGE) and M-value, and clinical characteristics of good, fair and poor control groups were compared.. The median MAGE and M-value was 6.6mmol/L and 18.7, respectively. Then MAGE >or=6.6mmol/L and M-value >or=18.7 was defined as poor control. In the 32 patients without detectable C-peptide levels, 18 patients (56%) showed poor control. The frequency of ketosis or ketoacidosis at onset of diabetes was dramatically higher in the poor control group not only in the patients as a whole but also in those without detectable C-peptide levels.. A decreased level of C-peptide is a significant factor in glycemic instability. However, some patients have glycemic stability though beta-cell function is completely depleted. The presence of ketosis or ketoacidosis at onset of diabetes may be a factor in later glycemic instability, suggesting the importance of examining patients in detail at onset of diabetes for careful follow-up to prevent progression of acute and chronic complications of diabetes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Homeostasis; Humans; Male; Middle Aged

To determine whether there are different rates of partial remission in preschool, school-age children, and adolescents with type 1 diabetes mellitus (T1DM) and to identify clinical characteristics that are associated with increased rate of partial remission.. A total of 152 consecutive patients with newly diagnosed T1DM in 2004 were studied. Clinical characteristics at diagnosis, hemoglobin A1C (HbA1C), and total daily insulin dose (TDD) at 3-month interval follow-up for 1 yr were analyzed in each age-group (group 1, aged <5 yr; group 2, aged 5-12 yr; and group 3, aged >12 yr). Partial remission was defined as TDD <0.5 units/kg/d with HbA1C <8% assessed at 6 months after diagnosis.. Young children (group 1, 26.8%) and adolescents (group 3, 29%) had low rates of partial remission compared with school-age children (group 2, 56%, p = 0.002). There were no differences in the rates of diabetic ketoacidosis (DKA), autoantibody frequency, and HbA1C at diagnosis between age-groups. DKA at diagnosis was associated with less likelihood of having partial remission (p < 0.001). There were no associations between gender, autoantibodies, and HbA1C at diagnosis and the rate of partial remission.. Young children and adolescent children with T1DM had a low rate of partial remission. Metabolic control was poorest in young children, whereas higher dose insulin in adolescents because of insulin resistance contributes to less likelihood of having partial remission. DKA at diagnosis was associated with low rate of partial remission. It is possible that the low frequency of honeymoon phase in young children reflects more aggressive beta-cell destruction in young children.

Topics: Adolescent; Bicarbonates; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Infant; Ohio; Remission Induction; Remission, Spontaneous; Risk Factors

All newly diagnosed diabetes in Kronoberg during 3 years was registered, with blood samples from 1630/1666 (97.8%) adults. Those positive for GADab and/or ICA and/or C-peptide<0.25nmol/L (0.7%) were classified as type 1 diabetes, the remaining as type 2. Incidence of type 1 in 0-19-year-olds was 37.8(36.1-39.6, 95%CI) and in 20-100 year-olds 27.1(25.6-27.4) per 100 000 and year, it was bimodal with equal peaks in 0-9 year-olds and in 50-80-year-olds. Adults had type 2 incidence 378 (375-380), children 3.1 (2.6-3.6). Among adults 6.9% had type 1 and 93.1% type 2. Among antibodypositive adults (n=101), GADab were present in 90%, ICA in 71%, both GADab and ICA in 61%. Ophthalmology contact as second source was confirmed for 98%. There were no gender differences in type 1 in any age group, small ones in pediatric subgroups. In type 2 men predominated in ages above 40 years. Incidences of type 1 diabetes in both children and adults were very high and as high above age 50 years as in children. Incidence of type 2 was the highest reported from Sweden, to which new diagnostic criteria, a high degree of case-finding, and many elders, may have contributed, but results may also reflect a true increase in incidence of both types of diabetes.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Autoantibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Sweden

Ketosis-prone diabetes (KPD) is a phenotypically defined form of diabetes characterized by male predominance and severe insulin deficiency. Neurogenin3 (NGN3) is a proendocrine gene, which is essential for the fate of pancreatic beta cells. Mice lacking ngn3 develop early insulin-deficient diabetes. Thus, we hypothesized that gender and variants in NGN3 could predispose to KPD. We have studied clinical and metabolic parameters according to gender in patients with KPD (n = 152) and common type 2 diabetes (T2DM) (n = 167). We have sequenced NGN3 in KPD patients and screened gene variants in T2DM and controls (n = 232). In KPD, male gender was associated with a more pronounced decrease in beta-cell insulin secretory reserve, assessed by fasting C-peptide [mean (ng/ml) +/- s.d., M: 1.1 +/- 0.6, F: 1.5 +/- 0.9; p = 0.02] and glucagon-stimulated C-peptide [mean (ng/ml) +/- s.d., M: 2.2 +/- 1.1, F: 3.1 +/- 1.7; p = 0.03]. The rare affected females were in an anovulatory state. We found two new variants in the promoter [-3812T/C (af: 2%) and -3642T/C (af: 1%)], two new coding variants [S171T (af: 1%) and A185S (af: 1%)] and the variant already described [S199F (af: 69%)]. These variants were not associated with diabetes. Clinical investigation revealed an association between 199F and hyperglycaemia assessed by glycated haemoglobin [HbA1c (%, +/-s.d.) S199: 12.6 +/- 1.6, S199F: 12.4 +/- 1.4 and 199F: 14.1 +/- 2.2; p = 0.01]. In vitro, the P171T, A185S and S199F variants did not reveal major functional alteration in the activation of NGN3 target genes. In conclusion, male gender, anovulatory state in females and NGN3 variations may influence the pathogenesis of KPD in West Africans. This has therapeutic implications for potential tailored pharmacological intervention in this population.

Topics: Adult; Anovulation; Basic Helix-Loop-Helix Transcription Factors; Biomarkers; Black People; C-Peptide; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Gene Expression; Genotype; Glucagon; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Nerve Tissue Proteins; Promoter Regions, Genetic; Sex Factors

A 64-years-old man referred to a hospital because of high-grade fever. He was diagnosed as having influenza B by "POCTEM Influenza A/B", a rapid influenza diagnostic kit which detect some antigens of influenza virus. Six days after medication of oseltamivir phosphate, his flu-symptoms disappeared, but he complained sever thirsty. And after 2days, he suffered from loss of consciousness and was admitted to the hospital. Laboratory data on admission showed diabetes ketoacidosis, slight elevation of HbA1c level despite sever hyperglycemia, and increase of serum amylase concentration. Anti GAD antibody and anti IA-2 antibody were not detected. Urinary C-peptide excretion was undetectable and serum C-peptide levels were also undetectable after glucagon and arginin load, suggesting disappearance of endogeneous insulin secretion. Class II HLA was susceptible to fulminant type1 diabetes. Based on these findings, we diagnosed him with fulminant type1 diabetes. In Japan, only three viruses in three cases have been reported to be the trigger in the development of fulminant type 1 diabetes. They were human herpes virus 6, herpes simplex virus and Coxsackie B3 virus. This is the fourth report of fulminant type 1 diabetes developed after the established diagnosis of viral infection and the first after influenza B virus infection. The fact that fulminant type 1 diabetes developed after the infection of such a common virus suggest that factors within host will play more important roles than virus itself in the etiology of fulminant type 1 diabetes.

Topics: Amylases; Antiviral Agents; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Hyperglycemia; Influenza B virus; Influenza, Human; Male; Middle Aged; Oseltamivir

'Fulminant diabetes' has been recognized as a super-acute onset and non-autoimmune type 1 diabetes. To evaluate autoimmunity against pancreatic beta cell in fulminant diabetes, ELISPOT assay was applied to the peripheral blood of these patients. In our ELISPOT system, GAD65-reactive and insulin B9-23-reactive IFN-gamma spots were detected in 46.3 and 26.0% of autoantibody-positive type 1 diabetes. Also, in fulminant type 1 diabetic patients, IFN-gamma spots in response to GAD65 and insulin B9-23 peptide were detected in 69.2 and 25.0%, respectively. These results suggest that anti-beta cell autoimmunity contributes to develop fulminant type 1 diabetes. Fulminant type 1 diabetes is known to have IDDM-resistant HLA DR2 with similar frequency of non-T1D subjects. In a mouse model, when islet-reactive CD8 cells are transferred to young NOD mice, the recipients develop overt diabetes within 1 week with massive insulitis. In (NOD x Balb/c) F1 mice, which hold idd-resistant genes, transfer of islet-reactive CD8 cells induced diabetes to 60% F1 recipients within 1 week with the later disappearance of insulitis. This mouse model shows very similar feathers to fulminant type 1 diabetes; idd-resistant HLA and no insulitis. These results implicated that once anti-islet immunity is optimally activated, subjects with partially resistant alleles could become overt diabetes.

Topics: Acute Disease; Animals; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Models, Animal; Humans; Insulin-Secreting Cells; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; T-Lymphocytes

Topics: Adult; Autoantibodies; B-Lymphocytes; C-Peptide; Diabetic Ketoacidosis; Female; Humans; Male; Predictive Value of Tests; Reproducibility of Results

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fasting; Humans; Insulin Resistance

To derive predictors of good glycaemic control in patients presenting with diabetic ketoacidosis (DKA) followed prospectively in a specialized clinic.. One hundred and sixty-one adult patients were admitted during a 31-month period and followed for at least 12 months. After 1 year, the patients were classified into three groups: good control (GC) (HbA1c < or = 7%), intermediate control (IC) (HbA1c 7-9%) and poor control (PC) (HbA1c > 9%). Characteristics of patients in the three groups were compared both at baseline and during follow-up.. At 12 months, 36% of the patients were classified as GC, 27% as IC and 37% as PC. GC patients had higher fasting serum C-peptide levels 0.7 +/- 0.54 compared to 0.38 +/- 0.29 and 0.16 +/- 0.21 nmol/l, respectively, for the IC and PC patients (p < 0.0001). A higher proportion GC patient had a C-peptide level greater than 0.33 nmol/l than that for IC and PC patients (86, 61 and 19%, respectively; p < 0.0001). Exogenous insulin was safely discontinued in 50, 30 and 3% of patients, respectively, in the GC, IC and PC groups (p < 0.0001). Compliance with life-style interventions was higher in the GC than that in IC and PC patients (87, 41 and 5%, respectively; p < 0.0001). In the logistic regression analysis, predictors of good glycaemic control were having baseline fasting serum C-peptide value > or =0.33 mmol/l, OR: 3.01 (95% CI 1.07-8.55, p = 0.03) and compliance with life-style interventions OR 12.66 (95% CI 3.73-51.57, p = 0.0001).. Among adult patients with DKA, significant predictors of good glycaemic control are preserved beta-cell function and compliance with life-style modifications.

Topics: Adult; Biomarkers; C-Peptide; Diabetic Ketoacidosis; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Logistic Models; Male; Middle Aged; Odds Ratio; Patient Compliance; Predictive Value of Tests; Prospective Studies; Treatment Outcome

Despite an increasing number of reports of ketoacidosis in populations with Type 2 diabetes mellitus, the pathophysiology of the ketoacidosis in these patients is unclear. We therefore tested the roles of three possible mechanisms: elevated stress hormones, increased free fatty acids (FFA), and suppressed insulin secretion.. Forty-six patients who presented to the Emergency Department with decompensated diabetes (serum glucose > 22.2 mmol/l and/or ketoacid concentrations > or = 5 mmol/l), had blood sampled prior to insulin therapy. Three groups of subjects were studied: ketosis-prone Type 2 diabetes (KPDM2, n = 13) with ketoacidosis, non-ketosis-prone subjects with Type 2 diabetes (DM2, n = 15), and ketotic Type 1 diabetes (n = 18).. All three groups had similar mean plasma glucose concentrations. The degree of ketoacidosis (plasma ketoacids, bicarbonate and anion gap) in Type 1 and 2 subjects was similar. Mean levels of counterregulatory hormones (glucagon, growth hormone, cortisol, epinephrine, norepinephrine), and FFA were not significantly different in DM2 and KPDM2 patients. In contrast, plasma C-peptide concentrations were approximately three-fold lower in KPDM2 vs. non-ketotic DM2 subjects (P = 0.0001). Type 1 ketotic subjects had significantly higher growth hormone (P = 0.024) and FFA (P < 0.002) and lower glucagon levels (P < 0.02) than DM2.. At the time of hospital presentation, the predominant mechanism for ketosis in KPDM2 is likely to be greater insulinopenia.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Epinephrine; Fatty Acids, Nonesterified; Glucagon; Human Growth Hormone; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Islets of Langerhans; Ketones; Middle Aged; Norepinephrine

To evaluate factors predictive of insulin discontinuation in subjects with ketosis-prone Type 2 diabetes.. One hundred and six subjects with ketosis-prone Type 2 diabetes were recruited during the index episode of diabetic ketoacidosis (DKA). All subjects were followed in a special clinic for at least 6 months. If the subject's glycaemic control reached specified glycaemic goals, exogenous insulin was gradually decreased until discontinuation. Baseline and follow-up characteristics were compared between the off-insulin and the on-insulin groups.. At the end of the follow-up period (915+/-375 days) insulin was discontinued in 47% subjects. Subjects in the off-insulin group were significantly older at the time of diagnosis of diabetes. In the off-insulin group the majority of subjects were newly diagnosed with diabetes. After 6 months of follow-up, subjects in the off-insulin group had significantly lower mean HbA(1c), higher mean C-peptide-to-glucose ratio and had more clinic visits per year. In the proportional hazard analysis, new-onset diabetes [hazard ratio (HR) 1.54; 95% confidence interval (CI) 1.02-2.45], and a higher C-peptide-to-glucose ratio at 6 months of follow-up (HR 1.77; 95% CI 1.22-2.63) were significant predictors of insulin discontinuation.. In subjects with ketosis-prone Type 2 diabetes, the best predictors of insulin discontinuation are having new-onset diabetes, and higher beta-cell functional reserve (as measured by the C-peptide-to-glucose ratio).

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans; Male; Middle Aged; Prospective Studies

C-peptide level is the most reliable factor evaluating the endogenous insulin secretion in patients with type 1 diabetes.. The aim of the study was to investigate whether the age at onset, gender, presence of autoantibodies and ketoacidosis at diagnosis and insulin requirement, HbA1c levels could be applied to predict the C-peptide levels in the first year of type 1 diabetes in children.. 122 type 1 diabetic children, aged: 2-18 years (average 11.2), 44 female and 78 male were studied. Fasting C-peptide levels were examined by radioimmunoassay at diagnosis, after 10 days and after 1, 2, 3, 6 and 12 months of disease. At diagnosis islet cell antibodies (ICA) were detected by indirect immunofluorescence, antibodies to glutamic acid decarboxylase (GADA) and tyrosine phosphatase antibodies (IA2A) were measured by microradioimmunoprecipitation assay.. Age at onset was positively correlated to C-peptide levels at each evaluated point of the disease (r=0.3-0.46, p<0.0001). One year after diagnosis C-peptide levels decreased in ICA(+) (p<0.04) and GADA(+) (p<0.002) patients but not in ICA(-) or GADA(-) children. There was no significant difference between the IA2A-positive and negative subjects in the C-peptide levels at 12th month of disease. C-peptide level was also related to ketoacidosis at diagnosis, insulin requirement and HbA1c levels during the first year of type 1 diabetes. Logistic regression analysis showed that male, younger age, low pH, higher HbA1c and insulin requirement at onset were associated with decreased C-peptide level at diagnosis (p<0.00002).. Young age, presence of diabetes-related autoantibodies and hyperglycaemia with severe acidosis at the disease onset may be associated with a decreased residual insulin secretion in type 1 diabetes in children.

Topics: Adolescent; Age Factors; Age of Onset; Autoantibodies; Biomarkers; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Progression; Female; Fluorescent Antibody Technique, Indirect; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Infant; Insulin; Insulin Antibodies; Male; Poland; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Radioimmunoprecipitation Assay; Time Factors

This study was designed to test the accuracy of capillary ketonemia for diagnosis of ketosis after interruption of insulin infusion.. A total of 18 patients with type 1 diabetes treated by external pump were studied during pump stop for 5 h. Plasma and capillary ketonemia and ketonuria were determined every hour from 7:00 A.M. (time 0 min = T0) to 12:00 P.M. (time 300 min = T300). Plasma beta-hydroxybutyrate (beta-OHB) levels were measured by an enzymatic end point spectrophotometric method, and capillary beta-OHB levels were measured by an electrochemical method (MediSense Optium meter). Ketonuria was measured by a semiquantitative test (Ketodiastix). Positive ketosis was defined by a value of >/=0.5 mmol/l for ketonemia and >/=4 mmol/l (moderate) for ketonuria.. After stopping the pump, concentrations of beta-OHB in both plasma and capillary blood increased significantly at time 60 min (T60) compared with T0 (P < 0.001), reaching maximum levels at T300 (1.30 +/- 0.49 and 1.23 +/- 0.78 mmol/l, respectively). Plasma and capillary beta-OHB values were highly correlated (r = 0.94, P < 0.0001). For diagnosis of ketosis, capillary ketonemia has a higher sensitivity and negative predictive value (80.4 and 82.5%, respectively) than ketonuria (63 and 71.8%, respectively). For plasma glucose levels >/=250 mg/dl, plasma and capillary ketonemia were found to be more frequently positive (85 and 78%, respectively) than ketonuria (59%) (P = 0.017). The time delay to diagnosis of ketosis was significantly higher for ketonuria than for plasma ketonemia (212 +/- 67 vs. 140 +/- 54 min, P = 0.0023), whereas no difference was noted between plasma and capillary ketonemia.. The frequency of screening for ketosis and the efficiency of detection of ketosis definitely may be improved by the use of capillary blood ketone determination in clinical practice.

Topics: 3-Hydroxybutyric Acid; Adult; Age of Onset; Blood Glucose; Blood Specimen Collection; C-Peptide; Capillaries; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Electrochemistry; Fingers; Humans; Insulin Infusion Systems; Ketone Bodies; Normal Distribution; Reagent Strips; Sensitivity and Specificity

We report two black adolescent subjects who presented with diabetic ketoacidosis, but who lacked autoimmune markers and demonstrated clinical and biochemical characteristics more typical of Type 2 diabetes, including obesity, acanthosis nigricans, positive family history for Type 2 diabetes, and Type 2 diabetic dyslipidaemia. Subsequent to acute presentation, insulin was discontinued in both subjects and excellent glycaemic control was achieved with metformin therapy alone. Four months following acute presentation, both had adequate C-peptide responses to intravenous glucagon. Type 2 diabetes can present as diabetic ketoacidosis in obese adolescent subjects.

Topics: Acanthosis Nigricans; Adolescent; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Metformin; Obesity

In some patients the ketoacidosis at the onset of type 1 diabetes has been observed.. The aim of this study was to investigate an effect of the clinical, genetic, immunological and metabolic parameters on the occurrence of ketoacidosis at the clinical onset of the disease.. 106 children with type 1 diabetes, aged 1.8-18.2 years (average 10.6), 40 female and 66 male, were studied. Diabetic ketoacidosis was defined as blood pH of less than 7.35 and severe acidosis as less than 7.2. Among the clinical features, age at onset of the disease and gender of patients were evaluated. Moreover, fasting C-peptide level, insulin requirement, HbA1c level, blood glucose level and body mass index normalized by age and sex were examined at the onset and 6, 12, 24 and 36 months after diagnosis. The HLA-DQA1 and DQB1 alleles and -23 HphI INS polymorphism and CTLA4 gene +49 polymorphism (PCR-RFLP) were studied and islet cell antibodies (ICA) as well as antibodies to glutamic acid decarboxylase (GADA) and thyrosine phosphatase antibodies (IA2A) were also determined.. The presence of diabetic ketoacidosis was observed in 55% and severe form in 9% of children. In the group of patients with ketoacidosis lower C-peptide level and lower c-peptide/glycaemia ratio than in children without ketoacidosis were observed (0.20+/-0.18 vs. 0.31+/-0.28 pmol/ml and 0.07+/-0.05 vs. 0.20+/-0.17, p<0.003, respectively). The patients with fasting C-peptide at the onset below normal range (<0.28 pmol/ml) were at high risk of ketoacidosis, OR (95%CI)=3.3 (1.3-8.2). The patients with ketoacidosis were characterized by higher exogenous insulin requirement than non-ketoacidosis individuals (1.2+/-0.6 vs. 0.8+/-0.5 j/kg/24h, p=0.004). Besides, in patients with severe ketoacidosis higher level of IA2A was found as compared to other patients (73.4+/-44.9 vs. 44.2+/-39.6; p=0.04). In this group more frequently 2 and/or 3 different autoantibodies were observed (90% vs. 79%), although, the difference was not significant.. The presence of diabetic ketoacidosis at clinical diagnosis of type 1 diabetes may be related to the residual b cell function, which is mainly determined by the intensity of immunological destruction.

Topics: Adolescent; Age Distribution; Age of Onset; Blood Glucose; Body Mass Index; C-Peptide; Child; Child, Preschool; Comorbidity; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Infant; Insulin; Male; Poland; Risk Factors; Sex Distribution

The purpose of the present study was to compare relationships between the clinical presentation of type 1 diabetes in children and residual beta-cell secretion and long-term metabolic control.. This retrospective study was conducted in 66 diabetic children with age at diagnosis ranging from 0.7 to 14.8 yr. The patients showed contrasting characteristics at diagnosis: either diabetic ketoacidosis (DKA) (group 1, n = 29) or absence of metabolic derangement (group 2, n = 37) associated with marked (group 2A, n = 12) or mild hyperglycemia (group 2B, n = 25). A regular follow-up was available for at least 10 yr (10-32 yr) in all cases and for 20 yr in 23 cases. C-peptide levels were measured from diagnosis and thereafter at intervals for the first years of disease until becoming permanently undetectable.. C-peptide levels at diagnosis were undetectable in about 20% of the cases both with and without DKA. C-peptide levels at diagnosis, the duration of measurable C-peptide levels and the maximum value found during follow-up were not significantly different in the three groups and were not correlated with glycated hemoglobin (GHb) calculated throughout the whole period. No differences were found between the groups of patients concerning GHb values and insulin dose at 10, 15 and 20 yr of disease. The patients of group 2A, characterized by an extremely high glycemic level without ketoacidosis, had a significantly higher prevalence of HLA DR3/4 heterozygosity.. The severity of clinical presentation at diagnosis does not significantly influence residual beta-cell function, and long-term metabolic control.

Topics: Adolescent; Adult; Blood; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glycated Hemoglobin; Heterozygote; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Hydrogen-Ion Concentration; Hyperglycemia; Islets of Langerhans; Retrospective Studies

The subject was a 26-year-old Japanese woman of 148 cm height, 96.2 kg of body weight (BW) (body mass index (BMI) of 43.8 kg/m(2)). She was referred to our hospital on May 1, 2000 for the evaluation of marked hyperglycemia with clinical symptom of general malaise, polydipsia, and ketonuria (3+). She did not smoke, or drink alcohol. But, she tended to eat lots of sweet food every day before the onset of this symptom. Her father was diagnosed type 2 diabetes mellitus. Her fasting plasma glucose and HbA(1c), and serum C-peptide were 398 mg/dl, 7.8% and less than 0.05 ng/ml [normal range: 0.94-2.8], respectively. She tested negative for anti-glutamic acid decarboxylase (GAD) antibodies and islet-cell antibodies. C-peptide level in her urine was as low as 3.4 microg/day. We immediately started insulin treatment under the diagnosis of abrupt onset of diabetes mellitus with diabetic ketoacidosis on the day of her admission, and the insulin treatment was continued after her being discharged. She showed continuous BW reduction until her BW reached approximately 60 kg, followed by her BW being plateau. During the period, intra-abdominal visceral fat (VF) and subcutaneous fat (SF) volume assessed by helical computerized tomography (CT) showed a substantial reduction [3.9-0.5 l for VF, 19-3.2 l for SF volume]. Pre-heparin plasma lipoprotein lipase (LPL) mass showed a considerably lower value when she had continuous BW reduction than did it when her BW reduction discontinued. These findings suggest that in this subject, continuous BW reduction after the abrupt onset of diabetes is closely associated with intra-abdominal fat mass reduction, which may be related to decreased production of LPL.

Topics: Adipose Tissue; Adult; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Insulin; Japan; Leptin; Lipids; Obesity; Regression Analysis; Tomography, X-Ray Computed

To determine differences between Black and White South Africans with diabetic ketoacidosis (DKA) and between Black patients on insulin vs. those on oral agents presenting with DKA, post stabilization fasting C-peptide levels and anti-glutamic acid decarboxylase (GAD) antibodies were measured together with serum glucose, acid base and urine ketones on admission. Of 60 patients with diabetic ketoacidosis (DKA) (76 admissions), the 43 Black patients had a higher BMI (23.1 vs. 20.0 kg/m(2), p=0.05) than did the 17 White patients, were more often newly diagnosed (37% vs. 1%, p=0.03), and a greater proportion of Black patients had fasting C-peptide levels >0.3 nmol/l (28% (10/36) vs. 0%, p=0.03). Of these 10 Black patients, eight were anti-GAD-negative. Thirteen Black patients (33%) were anti-GAD-positive vs. 10 (67%) White patients (p=0.03). There was no statistically significant difference in anti-GAD positivity between Black patients on oral agents or those on insulin. Most patients (5/7) admitted on oral agents had negative C-peptide levels after stabilization. Our results suggest that in patients presenting with DKA, a quarter of Black South Africans have C-peptide levels regarded as being indicative of type 2 DM and are less frequently anti-GAD-antibody-positive than are White South Africans.

Topics: Adult; Autoantibodies; Black People; Body Mass Index; C-Peptide; Chi-Square Distribution; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Glutamate Decarboxylase; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Prospective Studies; Statistics, Nonparametric; White People

Topics: Aged; Analgesics, Non-Narcotic; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; C-Peptide; Carbamazepine; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Eruptions; Female; Herpesviridae Infections; Herpesvirus 6, Human; Humans; Insulin; Insulin Secretion; Syndrome

A better understanding of the remission phase, while residual beta-cell function is still present in recently diagnosed type 1 (insulin dependent) diabetes mellitus (IDDM), is very important because of the potential for pharmacological intervention to preserve this function. To evaluate the natural course and characteristics of the remission phase in children and adolescents with IDDM, a retrospective study was performed on patients diagnosed with IDDM under the age of 18 years during the years 1991-1998. Sixty-two patients whose medical records were available were included in the study. Data were collected by reviewing the hospital records of patients from the time of diagnosis through the first 24 months after diagnosis. The duration of symptoms and history of infection prior to presentation, diabetic ketoacidosis (DKA) at diagnosis, length of hospitalization, initial glucose level, basal C-peptide levels at diagnosis, daily insulin requirements per kg body weight and HbA1c at diagnosis and at each visit were recorded. Thirty-five patients (56.5%) entered partial remission. We observed similar remission rates in those aged <10 and > or =10 years at diagnosis and in boys and girls. History of infection and presentation with DKA were associated with a lower rate of remission (p<0.001, p<0.0001, respectively) and were more commonly observed under the age of 10 years (p<0.0001, p<0.0001, respectively). The average insulin requirements per kg body weight calculated at diagnosis decreased with increasing age (r = -0.31, p = 0.012). The length of time until remission was 1.36+/-1.03 (mean +/- SD) months and positively correlated with insulin requirements at discharge from the hospital (r = 0.63, p<0.0001). Mean duration of remission was 11.67+/-5.82 months and was much longer in boys than girls (p<0.05). Six patients, all boys, entered total remission for 3.80+/-3.73 months. HbA1c concentrations in the first year of the disease were significantly lower in patients who underwent a remission phase (7.31+/-1.24% vs. 8.24+/-1.47%, p <0.05). However, this difference was not observed during the second year of the disease. In conclusion, history of infection prior to presentation and DKA at diagnosis were associated with young age and were the most important factors negatively influencing the remission rate in newly diagnosed IDDM patients.

Topics: Adolescent; Aging; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Infections; Insulin; Islets of Langerhans; Length of Stay; Male; Puberty; Remission Induction; Retrospective Studies

Topics: Addison Disease; Adolescent; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glucagon; Humans; Triglycerides

To test the hypothesis that there is lower prevalence of islet antibodies in subjects with newly diagnosed Type 1 diabetes mellitus in young adulthood than in children is associated with less severe diabetes at time of diagnosis.. This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of 15-34-year-old newly diagnosed diabetic subjects. During 1992-1993, all diabetic subjects (excluding secondary and gestational diabetes) were reported on standardized forms, with information about clinical characteristics at diagnosis. The study examined islet cell antibodies (ICA) by indirect immunofluorescence, and autoantibodies to glutamic acid decarboxylase (GADA), tyrosine phosphatase-like antigen (IA-2A) and insulin (IAA) as well as C-peptide by radioimmunoassay.. Blood samples were available from 78 patients with diabetic ketoacidosis (DKA) and 517 non-acidotic patients. The prevalence of ICA (63% vs. 57%), GADA (63% vs. 66%), IA-2A (35% vs. 44%) and IAA (20% vs. 15%) were very similar in patients with or without DKA. The median levels of the four autoantibodies did not differ between the two groups. High blood glucose (P < 0.001) and low C-peptide levels (P < 0.001) were the only parameters found to be related to DKA.. The similarities in findings of newly diagnosed diabetic patients with or without DKA regarding ICA, GADA, IA-2A and IAA suggest that there is no relationship between the expression of antigenicity and the severity of beta-cell dysfunction. The lower prevalence of the four autoantibodies in 15-34-year-old diabetic subjects compared with previous findings in children is not explained by misclassification of diabetes type.

Topics: Adolescent; Adult; Autoantibodies; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Fluorescent Antibody Technique, Indirect; Glutamate Decarboxylase; Humans; Incidence; Insulin Antibodies; Islets of Langerhans; Male; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 4; Receptors, Cell Surface; Sweden

To examine the clinical course, autoimmune status and pancreatic beta cell function, over a 2-year period, in young Chinese subjects newly presenting with diabetic ketoacidosis (DKA).. A prospective study involving 562 out of 27,893 patients who were admitted to the medical ward with a principal diagnosis of diabetes mellitus during the recruitment period of 1 year.. Of these 562 patients, 27 were aged less than 35 years and admitted with a diagnosis of DKA and 11 (six males and five females) of these were newly diagnosed. Antibodies to glutamic acid decarboxylase (GAD) were present in five patients. Anti-ICA 512 was not detected in any of the patients. Basal and post-glucagon stimulated plasma C-peptide remained in the insulin-deficient range although showing improvement at 2 years.. These findings confirm the relative rarity of autoimmune Type 1 diabetes in young Chinese. Even when the clinical presentation takes the extreme form of acute DKA, less than 50% have positive autoimmune markers.

Topics: Adult; Asian People; Autoantibodies; Blood Glucose; C-Peptide; China; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Follow-Up Studies; Glucagon; Glutamate Decarboxylase; Hong Kong; Humans; Islets of Langerhans; Male

To analyse among adult Caucasian patients hospitalised for diabetic ketoacidosis the relative frequency of patients with type 2 diabetes and their characteristics.. A retrospective review of adult patients presenting with diabetic ketoacidosis was conducted between 1993 and 1996. Patients with typical type 1 diabetes were classified according to age of onset < 35 years, insulin-dependence and BMI < 25 kg/m2; patients who did not meet these criteria were further classified on the basis of a basal and stimulated C-peptide and the detection of antibodies to glutamic acid decarboxylase (GADA) and to islet cells (ICA).. 43 patients presenting with an episode of diabetic ketoacidosis were divided into two groups, A and B. Group A consisted of 19 patients, 17 patients classified as patients with typical type 1 diabetes and 2 patients with diabetes post-pancreatectomy. The other patients were the subjects of our study (group B; n = 20, 4 lost to follow-up). 13 patients (65% of group B = B I) were diagnosed with type 1 diabetes (median basal C-peptide: 0.15 nmol/l) and 7 patients (35% of group B = B II) with type 2 diabetes (median basal C-peptide of 1 nmol/l). Higher body mass index (BMI), shorter duration of diabetes, smaller anion gap and worse glycaemic control were found to be significantly different between groups B I and II on admission (p < 0.05). After a median follow-up of 18 months, patients in group B II had a better metabolic control than those in B I and 5 of the 7 patients were treated without insulin.. Diabetic ketoacidosis is more common than previously thought in patients with type 2 diabetes, occurring in 16% of all cases. Distinctive features at presentation are the degree of acidosis, the duration of diabetes, BMI and HbA1c. However, the basal plasma C-peptide value remains the best discriminating factor.

Topics: Adult; Age of Onset; Autoantibodies; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Follow-Up Studies; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Male; Middle Aged; Pancreatectomy; Retrospective Studies; Switzerland; White People

To determine whether atypical diabetes mellitus (ADM) is present in the Chinese population in Hong Kong.. The records of Chinese patients who attended the Diabetes Clinic at Queen Mary Hospital were reviewed. We identified 11 patients who initially presented with acute diabetic ketoacidosis but subsequently displayed clinical features more typical of type 2 diabetes. Metabolic studies and HLA typing were performed to characterize this group of Chinese patients with ADM.. C-peptide response of the patients with ADM 1 h after a standard meal was intermediate between that of type 1 diabetic patients (matched for age and duration of diabetes) and that of nondiabetic control subjects (matched for age and BMI) (analysis of variance, P = 0.02). Insulin sensitivity measured by a short insulin tolerance test was not significantly different between patients with ADM and their matched nondiabetic control subjects. HLA typing showed that none of the patients with ADM had the DR3 allele and that the frequency of DR9 was not increased. Only one patient had significantly increased levels of antibodies to GAD and islet cell antigen 512.. ADM, which was first described in African-Americans, is seen also in Chinese subjects. These patients have significant residual C-peptide secretory capacity and should not be misdiagnosed and treated as patients with type 1 diabetes with life-long insulin therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; C-Peptide; China; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Histocompatibility Testing; HLA-DR3 Antigen; Hong Kong; Humans; Insulin; Male; Middle Aged; Retrospective Studies

Topics: Adult; Antipsychotic Agents; Benzodiazepines; C-Peptide; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Olanzapine; Pirenzepine

The prognostic significance of islet cell specific autoantibodies at the diagnosis of Type 1 (insulin-dependent) diabetes mellitus for the persistence of residual beta-cell function over the first 2 years of clinical disease was evaluated in a prospective population-based study. Seven hundred and eighty probands, aged 0.8-14.9 years, were examined for islet cell antibodies (ICA) and insulin autoantibodies (IAA), while 769 probands were studied for antibodies to glutamic acid decarboxylase (GAD65A). They were subsequently observed for 2 years. Lower serum C-peptide concentrations and higher requirement of exogenous insulin during the follow-up period were observed in the group of probands positive for at least one of the antibodies, especially for ICA or IAA. We conclude that the residual beta-cell function after the presentation of Type 1 diabetes is less in children initially positive for islet cell specific autoantibodies than in those testing negative at diagnosis. This might reflect possible heterogeneity in the pathogenesis of childhood diabetes. It also demonstrates that ICA and IAA negativity at the diagnosis of Type 1 diabetes is not associated with a smaller amount of functioning beta-cell mass, but the absence of antibodies probably reflects a slower beta-cell destructive process and a longer duration of preclinical disease.

Topics: Adolescent; Age Factors; Analysis of Variance; Antibody Specificity; Autoantibodies; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Finland; Follow-Up Studies; Glutamate Decarboxylase; Humans; Hydrogen-Ion Concentration; Hypoglycemic Agents; Infant; Insulin; Insulin Antibodies; Islets of Langerhans; Male; Prospective Studies; Sex Factors

An autoimmune basis for the pathogenesis of insulin-dependent diabetes mellitus (IDDM) is supported by the frequent presence of autoantibodies - islet cell antibodies (ICAs) and GAD antibodies (GADab). However, in Chinese patients with clinical IDDM, a low prevalence of ICAs was observed. In non-insulin-dependent diabetic (NIDDM) patients, it has been suggested that the presence of GADab may identify a subset of latent autoimmune diabetes in adults (LADA). We determined the frequency of GADab in a large group of 134 IDDM and 168 NIDDM Chinese patients, and assessed the relation with ICAs status. Results showed that 39.6% IDDM and 16.1% NIDDM patients had GADab, and 20.1% and 4.8%, respectively had detectable ICAs. Frequency of GADab positivity was not influenced by whether the patients had youth or adult-onset IDDM or NIDDM, or by duration of diabetes. NIDDM patients seropositive for GADab shared similar clinical characteristics and fasting C-peptide levels with those who were GADab negative. Presence of GADab therefore did not serve to identify a subgroup of patients with latent or slow-onset IDDM. Half (53%) of our IDDM patients had neither GADab nor ICAs. The reason for this observation is unclear. One theory is that other autoantigens yet to be identified may be contributory. Alternatively, in the Chinese, autoimmunity may not be the major factor in the pathogenesis of IDDM.

Topics: Adolescent; Adult; Autoantibodies; Body Mass Index; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Glutamate Decarboxylase; Humans; Islets of Langerhans; Male; Middle Aged; Singapore

Topics: Adolescent; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Coma; Diabetic Ketoacidosis; Glycated Hemoglobin; Humans; Insulin; Japan; Male; Obesity

Antibodies to glutamic acid decarboxylase (anti-GAD) and pancreatic beta cell secretory function were measured in 39 consecutive Chinese patients with a clinical diagnosis of insulin-dependent diabetes mellitus (IDDM) (19 males, mean +/- SD age. 37 +/- 15 years; body mass index (BMI), 22 +/- 4 kg/m2; mean duration of disease, 6.7 +/- 5.6 years). IDDM was defined on the basis of acute symptoms with heavy ketonuria (> 3+) or ketoacidosis at diagnosis, or requirement for continuous insulin treatment within one year of diagnosis. Insulin deficiency was defined as a post-glucagon stimulated plasma C-peptide concentration < or = 0.6 nmol/l. Overall, anti-GAD antibodies were positive (> 18 units) in 23% (n = 9) of these patients. Of the 39 patients, 29 (74%) were insulin deficient and 10 (26%) were non-insulin deficient. Anti-GAD antibodies were positive in 31% of the insulin-deficient patients but in none of the non-insulin-deficient group. Insulin deficiency and anti-GAD positivity were associated with younger age, earlier age of clinical onset and lower BMI. There were independent negative relationships between levels of anti-GAD antibodies and blood pressure and a positive relationship between insulin dosage and albuminuria. This study emphasises the difficulty in differentiating clinically between IDDM and NIDDM in Chinese patients. Despite the acute presentation, these patients had variable pancreatic beta cell secretory function. The varying duration of disease may partly explain the low prevalence of positive anti-GAD antibodies in these patients, but seems unlikely to explain fully the difference from Caucasian IDDM patients.

Topics: Adult; Australia; Autoantibodies; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; China; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Hong Kong; Humans; Insulin; Islets of Langerhans; Male; Regression Analysis

To determine the factors at diagnosis predictive of changes in residual beta-cell function and metabolic control in Type 1 diabetes, 125 patients older than 7 years of age consecutively diagnosed between March 1986 and June 1991 were followed prospectively for two years. The effect of age, gender and the presence of ketoacidosis (DKA) and islet-cell antibodies (ICA) on beta-cell function, metabolic control and insulin requirements were studied by multivariate analysis of variance (repeated measurements over time) in 90 patients who completed follow-up. DKA had an independent negative effect on residual beta-cell function over time (p = 0.001). ICA-positive patients had lower residual beta-cell function at the end of follow-up (p < 0.05), but overall differences were not significant. DKA and younger age had an independent negative influence on metabolic control (p < 0.05) and insulin requirements (p < 0.001) over time. It is concluded that residual beta-cell function in Type 1 diabetic patients two years after diagnosis was independently influenced by DKA and ICA at diagnosis. Moreover, DKA and age influenced metabolic control and could thus be used to predict those patients with rapidly deteriorating metabolic control who might benefit from a more intensive therapeutic approach.

Topics: Adolescent; Adult; Autoantibodies; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies

The frequency of insulin-dependent diabetes mellitus in the Turkish adult-onset diabetic population has not been assessed previously. In the present study, we retrospectively evaluated the medical records of 801 Turkish patients with adult-onset (> or = 30 years) diabetes to determine the frequency of cases diagnosed as insulin-dependent diabetes. Fifty-two (6.5%) patients met our criteria of adult-onset insulin-dependent diabetes mellitus. At disease onset, 20 patients presented with ketoacidosis (38.5%), while 32 patients (61.5%) were non-ketotic. In the insulin-dependent diabetic group, islet cell antibodies were positive in 10 out of 16 (62.5%) patients studied. In contrast, none of the 16 patients had positive reactions with respect to insulin autoantibodies. Twelve out of 20 patients (60%) had glucagon-stimulated C-peptide levels above 0.6 nmol/l, suggesting a sufficient insulin secretory reserve. In view of these observations, we conclude that insulin-dependent diabetes mellitus is not rare among patients with adult-onset diabetes in the Turkish population. In a majority of cases, the disease onset is non-ketotic. Beta-cell function is relatively preserved, and insulin autoantibodies do not develop at diagnosis. In contrast, islet cell antibodies are frequently present at the onset of clinical insulin-dependent diabetes, possibly indicating continuing beta-cell destruction.

Topics: Adult; Age Factors; Age of Onset; Autoantibodies; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glucagon; Humans; Incidence; Insulin Antibodies; Islets of Langerhans; Male; Medical Records; Middle Aged; Turkey

The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children.

Topics: Adolescent; Age Factors; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Administration Schedule; Educational Status; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Infant; Insulin; Islets of Langerhans; Male; Parents; Prognosis

This study was undertaken to find out how many current Korean patients with insulin dependent diabetes mellitus (IDDM) had a previous history of non-insulin requiring phase. Fasting serum C-peptide levels were measured in the 2300 diabetic patients during the visit to the Asan Medical Center, Seoul, Korea. Fifty-nine patients showed fasting serum C-peptide levels below 0.13 nmol/l. These 59 patients were classified further into two groups according to their history of insulin requirement: group A who required insulin within 1 year after diagnosis or presented initially as diabetic ketoacidosis and group B who had non-insulin requiring phase at least for 1 year (median: 5 years; range: 1-23 years). Twenty-six patients (44%) were classified into group A and 27 patients (46%) into group B. Median age of onset was 26 years (range: 10-50 years) and 45 years (range: 23-73 years) in groups A and B, respectively (P < 0.001). While the two groups had similar values in the current and maximum body mass indices, sex ratio and the prevalence of islet cell antibodies, 58% of the group A and 7% of the group B patients had histories of diabetic ketoacidosis. These results suggest a clinical heterogeneity in patients with IDDM in Korea.

Topics: Adolescent; Adult; Age of Onset; Aged; Body Mass Index; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Fasting; Female; Humans; Insulin; Korea; Male; Middle Aged

Our preliminary data indicate that 15% of African-American patients presenting with diabetic ketoacidosis (DKA) are obese. To determine underlying mechanisms, we analyzed the clinical characteristics and indexes of insulin secretion and insulin sensitivity in 35 obese patients with DKA, 22 obese patients with hyperglycemia, 10 lean patients with DKA, and 10 obese nondiabetic subjects. Studies were performed 1 day after resolution of DKA and after 12 weeks of follow-up. At presentation, both obese DKA and obese hyperglycemic patients had no detectable insulin response to intravenous glucose, but they did respond to glucagon administration. The acute insulin response (AIR) to glucagon in obese DKA patients (0.9 +/- 0.1 ng/ml, P < 0.01), but significantly greater than in lean patients with DKA (0.1 +/- 0.1 ng/ml, P < 0.01). After 12 weeks of follow-up, the AIR to glucose improved in both groups of obese diabetic patients but remained significantly lower than in nondiabetic control subjects (both P < 0.01). In contrast, the AIR to glucagon was not significantly different from that in obese control subjects. Insulin sensitivity was decreased in both groups of obese diabetic patients at presentation and improved after follow-up to levels similar to those in obese nondiabetic control subjects. Reactivity with islet cell antibodies was not detected in any of the patients. During follow-up, 25 of 35 obese DKA and 16 of 22 hyperglycemic patients were able to discontinue insulin therapy, with continued good metabolic control. Our results indicate that in African-Americans, obese patients with DKA represent a subset of type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Female; Georgia; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Reference Values; Thinness

The objective of this study is to understand the metabolic and immunologic basis of diabetes in adult blacks with diabetic ketoacidosis (DKA). Twenty-one black adults presenting with DKA ([mean +/- SD] blood pH = 7.18 +/- 0.09, plasma glucose = 693 +/- 208 mg/dl, and positive serum ketones) had a subsequent clinical course of non-insulin-dependent diabetes mellitus (NIDDM). Human leukocyte antigens (HLAs) DR and DQ and antibodies to glutamic acid decarboxylase (GAD) and islet cell cytoplasmic proteins (ICP) were measured to assess autoimmunity. Insulin action was evaluated by the euglycemic insulin clamp, and insulin secretion was measured by C-peptide responses to oral glucose. Ketoacidosis was treated with insulin. Two subjects had a precipitating illness; four had a history of NIDDM. At the time of study, subjects' glycemic control was good (HbA1c = 5.7 +/- 1.6%). Nine subjects were treated with insulin, and 12 were on either sulfonylurea treatment or diet alone. Men (n = 12) were younger than women (n = 9) (40.8 +/- 9.8 and 51.1 +/- 6.3 years of age, respectively, P < 0.05) but similar in body mass index (27.8 +/- 2.7 and 29.98 +/- 4.1 kg/m2, respectively). Antibodies to GAD and ICP were absent. All but one subject was insulin resistant compared with normal subjects (glucose disposal 3.56 +/- 0.04 vs. 6.86 +/- 0.02 mg.kg-1.min-1), and insulin secretion was lower. HLA DR3 and DR4 frequency was higher than in nondiabetic black control subjects (65 vs. 30%, P < 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autoantibodies; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Glucose Tolerance Test; Glutamate Decarboxylase; HLA-DQ Antigens; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Male; Middle Aged; Random Allocation; Reference Values; Sex Factors; White People

Topics: Adult; Blood Glucose; C-Peptide; Diabetic Ketoacidosis; Female; Fetal Death; Glucose Tolerance Test; Humans; Insulin; Pregnancy; Pregnancy in Diabetics

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Diabetic Ketoacidosis; Female; Fetal Diseases; Glucose Tolerance Test; Humans; Hydrocephalus; Pregnancy; Pregnancy Trimester, Second

Cytoplasmic islet-cell antibodies (ICA) and endogenous insulin secretion were studied in 46 Sudanese children (mean age 11.6 years) with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Islet-cell antibodies were detected both by the indirect immunofluorescence (IF) and complement fixation (CF) methods. Endogenous insulin levels were measured as C-peptide concentration using radio-immunoassays. The degree of metabolic control of diabetics was judged by the presence of diabetic ketoacidosis (DKA) at onset, glycated haemoglobin (HbA1c) level and insulin requirement, expressed as dose per kg body weight per day, at the time of presentation. Twenty-nine patients (63%) had either IF-ICA or CF-ICA or both in their sera. These figures are significantly higher than those reported for African populations. Islet-cell antibody positive patients had significantly lower C-peptide concentration, higher HbA1c level, higher insulin requirement and higher prevalence of ketoacidosis at presentation. Furthermore, the C-peptide levels were higher in CF-ICA positive patients than in subjects who showed only IF-ICA positivity. Our findings show a clear association between ICA and severity of diabetes at clinical onset and also suggest that the presence of CF-ICA at or shortly after diagnosis of IDDM is indicative of preservation of some functioning beta-cell mass.

Topics: Autoantibodies; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Fluorescent Antibody Technique; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Sudan

Cases of malnutrition-related diabetes mellitus conforming to the description of the protein deficient pancreatic diabetes type in Ethiopian patients were compared with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic. Fourteen of 39 malnutrition-related diabetes mellitus patients had fat malabsorption compared with only two of ten Type 1 diabetic patients and one of nine control subjects. Xylose absorption was normal favouring a pancreatic cause for the malabsorption. Plasma C-peptide during oral glucose tolerance test was significantly lower than that in Type 2 diabetic patients and normal control subjects (p less than 0.01 to 0.001) and was also consistently but not significantly higher than in Type 1 diabetic patients. Glucagon secretion patterns were similar in malnutrition-related and Type 1 diabetic patients. Of 23 new malnutrition-related diabetic patients treated with glibenclamide after nutritional rehabilitation and insulin treatment, only three responded, 14 were unresponsive but remained ketosis free for over eight days while another six developed ketoacidosis or significant ketonuria within two to six days during the trial. Sixteen unselected Type 1 diabetic patients who discontinued their insulin therapy all developed frank ketoacidosis after a mean of 5.5 days. The similarity of the malnutrition-related and Type 1 diabetes mellitus in age of onset, insulin requirement for diabetic control and appearance of ketosis-proneness in some cases, together with the similarity of C-peptide and glucagon secretion patterns suggest that the protein deficient pancreatic diabetes variant of malnutrition-related diabetes mellitus may be Type 1 diabetes mellitus modified by the background of malnutrition rather than an aetiologically separate entity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Ethiopia; Female; Glucagon; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Protein-Energy Malnutrition; Reference Values

This study was undertaken to evaluate whether differences in Type 1 diabetes incidence in two separate geographical locations are associated with any differences in biochemical and immunological features at the onset of the disease. We studied all children under 16 years of age who presented at the time of diagnosis with Type 1 diabetes to the children's hospitals in Oulu (n = 43) and Toronto (n = 87) during 1984-1985. At onset children from Northern Finland had lower blood glucose and HbAlc levels, and higher C-peptide concentrations than those from Southern Ontario (p's less than 0.01). The group from Northern Finland also had a higher incidence of multiplex families (18.6 vs 4.6%, p less than 0.01). Amongst the Finnish group, those from multiplex families had a higher C-peptide concentration and lower frequency of ketoacidosis than those from simplex families (p's less than 0.05). Thus differences do exist at the onset of diabetes in these groups from geographical locations with greatly different incidences of Type 1 diabetes.

Topics: Adolescent; Age Factors; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Finland; Glycated Hemoglobin; Humans; Hydrogen-Ion Concentration; Incidence; Infant; Infant, Newborn; Ontario

In order to characterize Type I diabetes at its clinical onset in French children, we studied HLA-DR alleles, beta-cell function and autoantibodies to islet-cell antigens and insulin in 115 patients aged 1.8-17 years. Beta-cell function was markedly impaired, but with an unexpectedly wide range of individual variations. These variations showed no correlation with HLA alleles or circulating autoantibodies, as opposed to observations made by others. Age, however, had a clear influence on the degree of impairment of residual insulin secretion, the younger children having the more deteriorated beta-cell secretory capacity conditioning the severity of clinical manifestations (weight loss, ketonuria, ketoacidosis) and initial hyperglycemia.

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; France; HLA-DR Antigens; Humans; Infant; Insulin Antibodies; Male; Polyuria; Weight Loss

To improve criteria for entry into future trials of immunosuppression, we enrolled 40 children with recent-onset Type I insulin-dependent diabetes in a pilot trial of cyclosporine. Twenty-seven patients were able to discontinue insulin therapy 48 +/- 5 days after the start of immunosuppression. At four months, their fasting and postprandial blood glucose concentrations averaged 110 and 160 mg per deciliter (6.1 and 8.9 mmol per liter) with a mean hemoglobin A1c level of 6.15 percent. Seventy-five percent of these patients with early remission still did not need insulin at 12 months, and their glycemic control was similar to that at 4 months. The major differences between the 27 patients with remission and the 13 without remission were the duration of symptoms before diagnosis (26.8 vs. 48.0 days, P less than 0.01), the degree of weight loss (3.2 vs. 10 percent of body weight, P less than 0.001), the initial hemoglobin A1c level (10.7 vs. 13.2 percent, P less than 0.001), and the frequency of ketoacidosis (11 vs. 61.5 percent, P less than 0.001). The lesser degree of weight loss was the strongest independent predictor of remission. The response of C-peptide to intravenous glucagon (0.50 vs. 0.17 pmol per milliliter, P less than 0.05) was also an independent predictor. No differences were observed between the two groups of patients in age, sex, HLA phenotype, autoantibodies to insulin or islet-cell antigens, or doses or trough levels of cyclosporine. Only minimal manifestations of toxicity were detected over the period of observation. We conclude that early treatment with cyclosporine in children with recent-onset Type I diabetes can induce remission from insulin dependence, with half the patients not requiring insulin after a full year.

Topics: Adolescent; Age Factors; Blood Glucose; Body Weight; C-Peptide; Child; Cyclosporins; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Insulin; Male; Pilot Projects; Remission Induction; Sex Factors; Time Factors

Thirty-four Arab patients with history of diabetes mellitus but without history of ketoacidosis (Group 2), and 16 Arab patients with history of diabetes mellitus and ketoacidosis (Group 1) were studied. They were compared with 15 healthy control subjects and were further broken down according to sex and type of therapy. Fasting serum C-peptide, glucose and glycosylated haemoglobin levels were measured in all subjects. C-peptide levels in Group 2 were higher (t = 2.95) and exhibited greater heterogeneity (Variance ratio 3.60, p less than 0.005) than those in Group 1. Female subjects in Group 2 were more obese than male subjects in the same group, and exhibited greater heterogeneity of their C-peptide levels (Variance ratio 9.47, p less than 0.001). Although male patients in Group 2 on insulin therapy were older than male subjects on diet or oral hypoglycemic agents (t = 3.52, p less than 0.01), female subjects on insulin therapy were younger than those on diet or oral hypoglycemic agents (t = 2.05, p less than 0.05). Furthermore female patients on insulin therapy had lower serum glycosylated haemoglobin levels than female subjects on oral hypoglycemic agents (t = 2.05, p less than 0.05) but male patients on insulin therapy had higher serum glycosylated haemoglobin than those on oral hypoglycemic agents. These data suggest the earlier tendency of physicians to prescribe insulin in women of child bearing age but suggest that earlier prescribing habits of insulin may improve diabetic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Kuwait; Male; Sex Factors

This study was undertaken to document clinical features and presentation of Type I diabetes and to study beta cell response in these patients. It provides data on 30 insulin treated patients. Type I diabetes presents most commonly in the 20-40 year age group. A positive family history in first degree relatives was noted in 40%. The commonest complications were retinopathy (63%) and peripheral neuropathy (53%). Proteinuria (10%), ischaemic heart disease (13%) and peripheral vascular disease (13%) were less common. Three kinds of response to C-peptide were noted: 1) no response 2) blunted response (below the normal range) and 3) peak response to glucose within the low normal range. Group 3 probably represents Type II insulin treated diabetes. There was poor correlation between fasting blood glucose and basal or peak C-peptide response, or with duration or complications of diabetes. C-peptide response may be used to differentiate Type I from Type II diabetes.

Topics: Adolescent; Adult; Aged; Antigen-Antibody Reactions; Antigens; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Fasting; Female; Humans; Insulin; Male; Middle Aged; Time Factors

Urine C-peptide per 24 h urine (UCPR) was assayed and correlated with the degree of insulin dependence in 324 diabetic patients. The UCPR and UCPR/weight were 74.7 +/- 26.3 micrograms/day and 1.27 +/- 0.36 micrograms/day, kg in healthy subjects, and these values were similar in diet- and sulfonylurea-treated patients. Insulin-dependent diabetics (IDDM) with history of ketosis or ketoacidosis and/or unstable plasma glucose, and patients refractory to sulfonylureas had lower UCPR values (8.5 +/- 6.6 and 22.3 +/- 14.6 micrograms/day) than the other insulin-treated patients (45.4 +/- 30.7 micrograms/day). In more than 90% of diet- and sulfonylurea-treated patients, UCPR exceeded 30 micrograms/day and UCPR/wt. exceeded 0.6 micrograms/day, kg. UCPR was less than 20 micrograms/day and UCPR/wt. less than 0.4 microgram/day,kg in more than 90% of IDDM patients, and less than 40 micrograms/day and 0.8 microgram/day,kg respectively in 80% of sulfonylurea-refractory patients. IDDM patients with more than 20 U/day of insulin doses had lower UCPR values. Longer duration of diabetes was associated with lower UCPR in IDDM patients. The results indicate that UCPR more than 30 micrograms/day or UCPR/wt. more than 0.6 micrograms/day,kg suggest non-insulin dependence, and UCPR less than 20 micrograms/day or UCPR/wt. less than 0.4 micrograms/day,kg suggest insulin dependence. Assay of UCPR provides a simple, non-invasive test for evaluating the degree of insulin dependence in diabetic patients.

Topics: Adolescent; Adult; Aged; Body Weight; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Humans; Insulin; Middle Aged; Sulfonylurea Compounds

An unusual case of factitious hypoglycaemia is described. The distinction between exogenous and endogenous hyperinsulinism is illustrated.

Topics: Adult; C-Peptide; Diabetic Ketoacidosis; Factitious Disorders; Humans; Hypoglycemia; Insulin; Male; Rural Population; South Africa

Diabetic hyperosmolar coma is a syndrome of marked hyperglycemia and minimal ketoacidosis. In general, the serum glucose concentrations are not predictive of the serum ketoacid concentrations in acutely decompensated diabetes. The endocrine factors that modulate glucose concentrations may be different from those that modulate ketoacid concentrations in patients with acutely decompensated diabetes. To test this hypothesis, regression analysis was used to determine the endocrine and metabolic characteristics that correlated with serum concentrations of glucose and ketoacids in 26 diabetic patients with spontaneous, acute hyperglycemia. All patients had a serum glucose level greater than 390 mg/dl, and ketoacid levels were from 0.17 to 25.5 mM. Multiple regression analysis showed that increased serum glucose concentrations correlated with increased plasma glucagon levels (p = 0.0007, r2 = 0.45), but with no other factors. Increased total ketoacid levels (acetoacetate plus 3-hydroxybutyrate) correlated with increased free fatty acid levels (p = 0.0001), decreased C-peptide levels (p = 0.002), and increased body mass index (p = 0.002) (r2 = 0.72). Body mass index only correlated with ketoacid levels, when it was analyzed with C-peptide and free fatty acid levels. A model is proposed that predicts the serum glucose and ketoacid concentrations in patients with acutely decompensated diabetes. Glucagon modulates the serum glucose concentration in these patients with an absolute or relative insulin deficiency. Total serum ketoacid levels are determined by the serum free fatty acid concentration, residual pancreatic insulin secretion (as reflected by C-peptide), and the patient's body habitus. This model allows for the marked hyperglycemia and minimal ketosis of diabetic nonketotic hyperosmolar coma, as well as the glucose and ketoacid concentrations in other presentations of acutely decompensated diabetes.

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetic Coma; Diabetic Ketoacidosis; Fatty Acids, Nonesterified; Female; Glucagon; Growth Hormone; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Keto Acids; Male; Middle Aged; Models, Biological; Regression Analysis

A 17-year-old boy with pituitary gigantism who had two episodes of diabetic ketoacidosis is reported. Glucose tolerance and insulin secretion were evaluated before, during and after each episode of ketoacidosis. The patient was 201 cm tall and weighed 137 kg. Before surgery, his plasma growth hormone level was 3,000 ng/ml, glucose tolerance was almost normal and insulin response to glucose load was enhanced. He fell into diabetic ketoacidosis twice; 3 weeks after hypophysectomy and one year later after getting the "flu". On each occasion, insulin treatment was needed only temporarily. After the ketoacidosis improved, glucose tolerance and C-peptide responses became nearly normal. Urine C-peptide was low during and immediately after the second episode, but increased to normal following recovery. It is presumed that a pre-operative compensation for the diabetogenic action of excess growth hormone by hyper-secretion of insulin was broken when superimposed stress was added. This is an example in which subnormal insulin response may not be a prerequisite for the occurrence of a severe diabetic state, and decompensated insulin secretion leading to ketoacidosis may not imply permanent damage to the beta cells.

Topics: Adolescent; C-Peptide; Diabetic Ketoacidosis; Gigantism; Glucose Tolerance Test; Growth Hormone; Humans; Hypophysectomy; Insulin; Male; Pituitary Hormones, Anterior; Thyrotropin-Releasing Hormone

Diabetic ketoacidosis is an extremely rare manifestation of glucagonoma. We report such a case in a 72-year-old woman known to be diabetic for seven years. The patient was admitted with diabetic ketoacidosis and associated necrolytic migratory erythrema which suggested the diagnosis of glucagonoma. Plasma glucagon levels were increased (569 to 2298 pg/ml). A vascular tumor of the head of the pancreas without obvious hepatic metastases was visualised by angiography. Duodeno-pancreatectomy including the head of the pancreas led to complete recovery of the mucocutaneous lesions and the plasma glucagon level fell (229 pg/ml). The tumor had several histological characteristics suggesting malignancy and a high glucagon content on extraction. Electron microscopy showed multiple A cells and a few isolated B cells. Most of the cells showed immunoreactivity with anti-glucagon and anti-glicentine antibodies. Three months after surgery, the diabetes was again required treatment with insulin. Plasma glucagon level was again increased and chemotherapy with dimethyltriazenimidazolecarboxamide was undertaken.

Topics: Adenoma, Islet Cell; Aged; Blood Glucose; C-Peptide; Diabetic Ketoacidosis; Female; Glucagon; Glucagonoma; Humans; Pancreatic Neoplasms

A clinical syndrome, characterized by acute diabetic ketoacidosis associated with a toxic neuropathy, developed in five men who intentionally ingested a recently introduced rodenticide (Vacor) containing N-3-pyridylmethyl-N'-p-nitrophenyl urea (RH-787). A 7-yr-old boy, who accidentally ingested this poison, died within 14 h. Marked insulinopenia, without a reduction in glucagon levels, suggested a specific beta-cytotoxic effect, which was supported after autopsy in three cases by histopathologic evidence of extensive beta cell destruction. Lethal effects in rats prevented investigation of RH-787's diabetogenicity in vivo; however, studies in isolated rat islets confirmed a direct inhibitory effect, which was prevented by concomitant incubation with nicotinamide, suggesting a mechanism of action similar to that of streptozotocin. We detected islet cell-surface antibodies in two of four patients studied. These findings indicate that this nongenetic, acquired form of insulinopenic diabetes, which has persisted in the surviving patients for up to 3 yr, presents a unique opportunity to test in man the concept that hyperglycemia and the accompanying metabolic consequences of insulinopenia can induced diabetic microangiopathy in the absence of genetic predisposition.

Topics: Adult; Arginine; Blood Glucose; C-Peptide; Child; Diabetes Mellitus; Diabetic Ketoacidosis; Diabetic Neuropathies; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Phenylurea Compounds; Tolbutamide

Topics: Adolescent; Adult; Aged; Aldosterone; Blood Glucose; C-Peptide; Dehydration; Diabetic Ketoacidosis; Epinephrine; Female; Glucagon; Growth Hormone; Humans; Hydrocortisone; Hyperglycemia; Insulin; Male; Middle Aged; Norepinephrine; Pancreatic Polypeptide; Parathyroid Hormone; Prolactin

Topics: Blood Coagulation Disorders; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Ketoacidosis; Diabetic Retinopathy; Glucagon; Hemoglobin A; Humans; Insulin; Insulin Secretion

Nine of ten non-obese non-ketotic diabetics attending Port Moresby General Hospital had detectable C-peptide in plasma. All had received insulin for at least two months at the time of study. It is concluded that many non-obese non-ketotic young diabetics in Papua New Guinea retain pancreatic insulin secretion and so resemble the maturity onset diabetics of "Western" countries.

Topics: Adolescent; Adult; Body Weight; C-Peptide; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Humans; Insulin; Insulin Secretion; Male; New Guinea

Topics: Adolescent; Adult; C-Peptide; Diabetic Ketoacidosis; Female; Glucagon; Glucose; Growth Hormone; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Tolbutamide

A group of 58 diabetics, age 6-17 years and with a duration of diabetes of 3-14 years was studied in order to show whether the nature of the clinical manifestations and the treatment at the onset of the disease are related to the subsequent C-peptide production and also whether remaining C-peptide production is related to better diabetic control. The relations between a number of clinical and laboratory variables were analysed including the degree of ketosis and the insulin dose given at onset of diabetes, the incidence of postinitial remission period, the fasting C-peptide level after the remission period, the level of insulin antibodies and the actual diabetic control expressed as the degree of glucosuria in the patients' urine tests at home. Multiple regression analysis was the main method used. Postinitial remission was positively correlated to initial insulin dose and negatively correlated to duration of ketonuria at onset. C-peptide, which was found in 24.1% of the patients was positively correlated to age at onset and initial insulin dose, but negatively correlated to ketonuria at onset. Diabetic control was positively correlated to insulin dose at onset and to C-peptide level, but negatively correlated to insulin antibodies. It could further be shown that patients who had received a more vigorous treatment immediately at onset had both a higher incidence of postinitial remission and a better diabetic control. The results suggest that an early diagnosis followed by rapid normalization of the metabolism at the onset of juvenile diabetes increase the possibility of preservation of some of the endogenous insulin production, which seems to facilitate diabetic control.

Topics: Adolescent; Age Factors; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycosuria; HLA Antigens; Humans; Insulin; Insulin Antibodies; Ketone Bodies; Male; Peptides; Regression Analysis; Remission, Spontaneous; Time Factors

"Essential labile diabetes" is an insulin-dependent diabetes, in the course of which irregular and unpredictable hyperglycemias, frequently with ketosis, and sometimes serious hypoglycemias alternate. In spite of careful treatment with insulin, diet and suitable hygienic measures, this form of diabetes cannot be influenced. Fortunately, it seldom occurs, not more frequently than in 1 to 2% of diabetics. Various attempts have been made to explain the pathogenesis of this form of the disease. The most probable explanation is that there is an almost complete exhaustion of insulin secretion. This hypothesis is based on the extremely low level of the C peptide below 0.60 ng/ml, whereas in non-labile insulin-dependent diabetics the C peptide amounts to more than 2.2 ng/ml

Topics: Activities of Daily Living; Adult; Arginine; C-Peptide; Diabetes Mellitus; Diabetic Ketoacidosis; Diagnosis, Differential; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Hypoglycemia; Insulin; Insulin Secretion; Male; Middle Aged