c-peptide and Remission--Spontaneous

This prospective pilot study was undertaken to test the efficacy of oral methyl-prednisolone (MP) therapy at spontaneous remission phase of type 1 diabetes in intervening the course of the disease. Twenty-five type 1 diabetic patients who were classified as having a spontaneous remission (honeymoon) were divided into treatment and non-treatment groups on voluntary basis. Fifteen patients thus making up the treatment group (13 males and 2 females, mean age 23.8 +/- 6.2 years) received 0.7-1.0 mg/kg/day of MP p.o. for 2 weeks. The dose of the drug was then gradually diminished every week until 5 mg/day (approx. 0.1 mg/kg/day) and discontinued at 10 +/- 2 weeks. In case of hyperglycemia occurring in 12 of 15 patients due to the administration of steroid, insulin was used to normalize blood glucose levels (average 0.47 +/- 0.21 IU/kg/day). The non-treatment group (8 males and 2 females, mean age 21.8 +/- 8.9) did not receive any special medication or placebo except for insulin whenever necessary to regulate glycemia. Upon completion of protocol, all patients in treatment group displayed clinical remission with 10 still in non-insulin requiring remission for follow-up periods ranging between 16 and 91 months. The remaining 5 patients relapsed within 3-15 months of therapy. Other metabolic (including basal and stimulated C-peptide levels) and immunological indices that have spontaneously ameliorated with the occurrence of honeymoon were also maintained within normal range in the NIR patients. Meanwhile, natural remission in the non-MP-treated group terminated at 3.4 +/- 0.6 months with deterioration of all metabolic and immunological markers as well as increasing requirements for insulin. In conclusion, the spontaneous remission of the patients could be prolonged significantly by MP therapy as opposed to no therapy (P < 0.001). These results suggest that the spontaneous remission phase may be a crucial point of intervention in immunotherapy of type 1 diabetes and that randomized trials with MP at this particular phase would be worthwhile.

Topics: Adult; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Follow-Up Studies; Glycated Hemoglobin; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Islets of Langerhans; Male; Methylprednisolone; Pilot Projects; Prospective Studies; Remission, Spontaneous; T-Lymphocytes

To describe the natural course of clinical remission in insulin-dependent diabetes mellitus (IDDM) when insulin dose is minimized without loss of target glycemia and to identify factors that predict clinical remission.. Ninety-five patients, who were placebo-treated control subjects in the Canadian-European multicenter randomized trial of cyclosporin A in recent-onset IDDM, were studied.. The mean insulin dose decreased during the first months after diagnosis, with a nadir at 3 mo, when 27% of the patients did not require insulin to maintain target glycemia. At 1 yr, 10% of patients still did not need insulin. Patients not receiving insulin who had glycosylated hemoglobin within the normal range were called remitters. Mean basal and glucagon-stimulated C-peptide values were significantly (P less than 0.025) higher in remitters than nonremitters at the start of the study. Therefore, all patients were divided into those with values above the mean stimulated C-peptide (0.4 nM) and those with values below the mean at entry. The probability of entering a remission with a stimulated C-peptide greater than 0.4 nM was 10 times as high (P less than 0.05) as for those with a stimulated C-peptide below this level. Surprisingly, the beginning and end of the remission were associated with neither major changes in C-peptide levels nor islet cell antibody and insulin-antibody titer. A more rapid loss of stimulated C-peptide occurred in patients who lacked HLA-DR3 and -DR4 (P less than 0.05 at mo 9).. This study shows a higher spontaneous clinical remission rate than expected during the 1st yr after diagnosis. Preserved beta-cell function at entry predicts a greater chance of entering a remission, and a more rapid loss of beta-cell function was seen in patients without HLA-DR3 and -DR4.

Topics: Adult; Autoantibodies; Blood Glucose; C-Peptide; Cyclosporine; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glucagon; Glycated Hemoglobin; Humans; Insulin; Insulin Antibodies; Islets of Langerhans; Male; Probability; Remission, Spontaneous

15 insulin-dependent diabetic children at onset were randomly allocated to one of two different therapeutical protocols: continuous subcutaneous insulin infusion (CSII) and intensified conventional insulin treatment with three daily insulin injections (CIT). Both treatments were performed for 10 days; the initial insulin dose was 1.5 U/kg/day and thereafter the insulin dosage was modified in order to obtain a satisfactory control. Near-normal blood glucose levels were obtained after 24 h in the CSII group, and after 3 days in the CIT group. All subjects underwent 1 year of follow-up. HbA1 levels and insulin requirements decreased similarly in the two groups; C-peptide secretion did not increase significantly in both groups. A clear advantage of CSII cannot be assumed, and the usefulness of this therapeutical approach needs to be confirmed by further investigations.

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin; Insulin Infusion Systems; Male; Remission, Spontaneous

Currently, there is a lack of data relating to glycemic parameters and their relationship with C-peptide (CP) and proinsulin (PI) during the partial remission period (PRP) in type 1 diabetes mellitus (T1D). The aim of this study was to evaluate glycemic parameters in children with T1D who are in the PRP using intermittently scanned continuous glucose monitoring systems (isCGMS) and to investigate any relationships between CP and PI levels.. The study included 21 children who were in the PRP and 31 children who were not. A cross-sectional, non-randomized study was performed. Demographic, clinical data were collected and 2 week- isCGMS data were retrieved.. The Serum CP showed a positive correlation with time-in-range in the PRP (p:0.03), however PI showed no correlations with glycemic parameters in both periods. The Serum CP and PI levels and the PI:CP ratio were significantly higher in the PRP group than in the non-PRP group. In the non-PRP group, the PI level was below 0.1 pmol/L (which is the detectable limit) in only 2 of the 17 cases as compared with none in the PRP group. Similarly, only 2 of the 17 children in the non-PRP group had CP levels of less than 0.2 nmol / L, although both had detectable PI levels. Overall time-in-range (3. 9-1.0 mmol/L) was significantly high in the PRP group. In contrast, the mean sensor glucose levels, time spent in hyperglycemia, and coefficient of variation levels (32.2vs 40.5%) were significantly lower in the PRP group.. Although the mean glucose and time in range during the PRP was better than that in the non-PRP group, the glycemic variability during this period was not as low as expected. While the CP levels showed an association with TIR during the PRP, there was no correlation between PI levels and glycemic parameters. Further studies are needed to determine if PI might prove to be a useful parameter in clinical follow-up.

Topics: Adolescent; Blood Glucose; Blood Glucose Self-Monitoring; C-Peptide; Child; Child, Preschool; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Proinsulin; Remission, Spontaneous

To explore the different patterns of C-peptide decline in patients with and without partial remission of newly diagnosed type 1 diabetes (T1D).. A total of 298 patients with new-onset T1D were followed up regularly at 3 months' interval to investigate the loss of C-peptide. Partial remission was determined by postprandial C-peptide ≥300 pmol/L or insulin dose-adjusted A1c ≤ 9 in the absence of C-peptide. Beta-cell function was defined as preserved, residual or failed by postprandial C-peptide of ≥200 pmol/L, 50-200 pmol/L or ≤50 pmol/L, respectively.. Altogether, 199 out of 298 patients (125 adults) had partial remission. The pattern of C-peptide change in patients with partial remission was three-phasic, demonstrating an upward trend followed by a downward trend of fast first and then slow, while the pattern in patients without partial remission was biphasic, showing an initial fast fall and a subsequent slower decrease. The patterns remained consistent when patients were stratified by the age of onset. At 3 years, there were 71% of the patients with partial remission still had preserved or residual beta-cell function, while 89% of the patients who had no partial remission developed beta-cell function failure. In patients whose partial remission ended, the average C-peptide was still higher than duration-matched patients without partial remission.. Patients with partial remission of T1D have a distinct three-phasic pattern of C-peptide decline, other than the widely recognized biphasic pattern. The effect of partial remission still exist​s after remission ends.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin-Secreting Cells; Remission, Spontaneous

Topics: Adolescent; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Exercise; Glycated Hemoglobin; Humans; Infant; Remission, Spontaneous

BACKGROUND This study aimed to determine the frequency and duration of remission in children and adolescents newly diagnosed with type 1 diabetes and to investigate factors associated with these parameters. MATERIAL AND METHODS Fifty patients newly diagnosed with T1DM were followed for 1 year. Daily insulin requirement of less than 0.5 U/kg/day dose when the HbA1c value is less than 8% was regarded as partial remission. Patients were grouped according to their remission duration. Clinical and laboratory characteristics of the remission groups and non-remission groups were compared to find factors influencing remission and to investigate their contribution to the duration of remission. RESULTS Remission was observed in 24 (48%) out of 50 patients included in the study. Remission frequency was found to be associated with age, sex, and puberty. Longer duration of remission was more frequent in the younger age group, in pre-pubertal stage, and in male patients. Daily insulin dose and basal insulin requirement of those who went into remission was found to be significantly lower than in the other patients at discharge. CONCLUSIONS Decreased daily total and basal insulin requirement at discharge are valuable in predicting remission. The remission process in type 1 diabetes still has many characteristics that need to be clarified. Therefore, more extensive studies are needed.

Topics: Adolescent; Age Factors; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Disease-Free Survival; Female; Glycated Hemoglobin; Humans; Insulin; Male; Remission Induction; Remission, Spontaneous; Sex Factors; Sexual Maturation; Time Factors

Proinsulin is a marker of beta-cell distress and dysfunction in type 2 diabetes and transplanted islets. Proinsulin levels are elevated in patients newly diagnosed with type 1 diabetes. Our aim was to assess the relationship between proinsulin, insulin dose-adjusted haemoglobin A1c (IDAA1C), glucagon-like peptide-1 (GLP-1), glucagon, and remission status the first year after diagnosis of type 1 diabetes.. Juvenile patients (n = 275) were followed 1, 6, and 12 months after diagnosis. At each visit, partial remission was defined as IDAA1C ≤ 9%. The patients had a liquid meal test at the 1-, 6-, and 12-month visits, which included measurement of C-peptide, proinsulin, GLP-1, glucagon, and insulin antibodies (IA).. Patients in remission at 6 and 12 months had significantly higher levels of proinsulin compared to non-remitting patients (p < 0.0001, p = 0.0002). An inverse association between proinsulin and IDAA1C was found at 1 and 6 months (p = 0.0008, p = 0.0022). Proinsulin was positively associated with C-peptide (p < 0.0001) and IA (p = 0.0024, p = 0.0068, p < 0.0001) at 1, 6, and 12 months. Glucagon (p < 0.0001 and p < 0.02) as well as GLP-1 (p = 0.0001 and p = 0.002) were significantly lower in remitters than in non-remitters at 6 and 12 months. Proinsulin associated positively with GLP-1 at 1 month (p = 0.004) and negatively at 6 (p = 0.002) and 12 months (p = 0.0002).. In type 1 diabetes, patients in partial remission have higher levels of proinsulin together with lower levels of GLP-1 and glucagon compared to patients not in remission. In new onset type 1 diabetes proinsulin level may be a sign of better residual beta-cell function.

Topics: Adolescent; Age of Onset; Blood Glucose; C-Peptide; Child; Child, Preschool; Cohort Studies; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Glucagon; Glucagon-Like Peptide 1; Humans; Infant; Infant, Newborn; Male; Proinsulin; Remission, Spontaneous

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

The aim of the study was to identify individual, clinical and metabolic factors that predict the C-peptide levels and appearance of clinical partial remission during the first year of type 1 diabetes (T1D) in children.. 197 type 1 diabetic patients (84 female and 113 male, mean age 10.4 years) were examined. C-peptide levels were detected by radioimmunoassay at the diagnosis and after 3, 6 and 12 months of the disease.. Median C-peptide level at onset was 0.17 pmol/mL (0.11-0.32), peaked in the 3rd month (0.27 pmol/mL, 0.15-0.43; p<0.001) and declined thereafter - 0.21 pmol/mL (0.1-0.34) in the 6th month and 0.13 pmol/mL (0.05-0.26) at the 12th month of the disease. Logistic regression showed that younger age, low pH and higher HbA1c (glycated haemoglobin) at the onset were associated with the "lower" (<0.28 pmol/mL) C-peptide level at the diagnosis. The presence of clinical partial remission was observed in 31% of children. Patients with remission had higher C-peptide levels observed in the first 6 months of T1D than children without clinical remission. Receiver operating characteristic (ROC) curve method was used for the estimation of the threshold of C-peptide level at the onset for the prediction of the clinical remission during the first year of T1D (0.141 pmol/mL, AUC (95%CI) = 0.608 (0.53-0.68)).. Concluding, higher C-peptide level is associated with the appearance of clinical partial remission during the first six months of T1D. C-peptide level may be a good predictor of the clinical partial remission during the first year of T1D.

Topics: Adolescent; Age of Onset; Biomarkers; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Fasting; Female; Glycated Hemoglobin; Humans; Infant; Male; Prognosis; Radioimmunoassay; Remission, Spontaneous; ROC Curve; Time Factors

A 53-year-old Caucasian woman presented with repeated episodes of hypoglycemia. Self-monitored blood glucose levels during the attacks were between 40 and 60 mg/dl (2.2-3.3 mmol/l).. An oral glucose tolerance test performed over 210 minutes showed normal baseline glucose levels, markedly elevated levels of serum insulin and slightly elevated C-peptide concentrations. During the test, a marked increase of insulin and a normal increment of C-peptide were observed. The tentative diagnosis of an insulinoma was raised and a 72 h fasting test performed, throughout which the insulin-glucose-ratio was pathologically elevated, whereas C-peptide levels were only slightly elevated.. Strongly positive levels of insulin antibodies led to the diagnosis of an insulin autoimmune syndrome.. This syndrome is caused by IgG-insulin-complexes with prolonged plasma half-life in the presence of reduced insulin action. The therapy consisted of fractionated meals to avoid hyperinsulinism and following hypoglycemic episodes. After four months a spontaneous clinical remission was observed.. The autoimmune insulin syndrome is a rare cause of recurrent, spontaneous hypoglycemia in Europe in non diabetic patients. Its prognosis is good as there is a high rate of spontaneous clinical remission in up to 80 % of patients.

Topics: Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Hypoglycemia; Immunoglobulin G; Insulin; Insulin Antibodies; Middle Aged; Prognosis; Remission, Spontaneous; Syndrome

Although it is well known that patients with type 1 diabetes mellitus are susceptible to other autoimmune diseases, the simultaneous occurrence of clustered distinct autoimmune diseases is uncommon. We report a 16-year-old girl, previously diagnosed as having coeliac disease and IgA deficiency, who at 13 years of age developed a clustering of distinct autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis (RA) and euthyroid autoimmune thyroiditis, eventually resulting in a simultaneous long-term remission. The clinical picture was associated with a functional immunodeficiency characterized by a defect in proliferative responses to T cell predominant mitogens and a normal response to the B cell predominant mitogen. In addition, the T cell activation markers HLA-DR, IL-2 receptor and transferrin receptor) were not upregulated. The clinical course of this immunodeficiency paralleled the outcome of the autoimmune diseases. After the abrupt onset, spontaneous clinical remission of both diabetes mellitus and RA was observed. Insulin was first reduced in dose and then discontinued completely at 15 months, in the presence of normal C peptide secretion and normal metabolic control (HbA1c 5.8%). Anti-glutamate decarboxylase (GAD65) and anti-IA-2 antibodies remained persistently high. During the remission phase a normalization of the functional immune defect was observed. The gradual resolution of the multisystemic diseases as well as the normalization of immune function in our patient is unusual. This case may be of considerable value in furthering our knowledge of the immunological mechanisms implicated in these rare multireactive syndromes.

Topics: Adolescent; Arthritis, Rheumatoid; Autoantibodies; C-Peptide; Celiac Disease; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Female; Glucose Tolerance Test; Humans; IgA Deficiency; Mitogens; Remission, Spontaneous; Thyroiditis, Autoimmune; Up-Regulation

To analyze factors contributing to a long-term remission in a patient with type I diabetes.. The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and beta-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects.. Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr.. In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.

Topics: Adolescent; Autoantibodies; Blood Glucose; Body Composition; C-Peptide; Cyclosporine; Diabetes Mellitus, Type 1; Follow-Up Studies; Glucose; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans; Male; Proinsulin; Remission, Spontaneous

It seems rational to consider that residual insulin secretion is one of the factors which determine the short-term course of inaugural type I diabetes. But what about the mid-term course? We evaluated prospectively the insulin reserve (fasting and post-prandial C peptide) in 52 patients throughout the subsequent development of the disease. The patients (36 men, 16 women, mean age 35 years), who presented with ketonuria and weight loss, received a 10-day course of intensive insulin therapy, after which a remission of insulin dependence was observed in 40 of them (77 per cent). These 40 patients differed from those who had no such remission in that they were heavier and had a better initial insulin secretion. There was no significant difference between the two groups with regards to immunogenetic markers (presence of anti-islet antibodies 28/35 vs 8/12, DR3 and/or DR4 tissue group 27/37 vs 8/10). Following intensive insulin therapy, the C peptide value was consistently increased. At 6, 12 and 18 months the insulin secretion in patients of the remission group remained stable and always higher than that of patients who did not have a remission and whose insulin secretion collapsed at 18 months. Another characteristic of the remission group was that C peptide secretion could be stimulated by meals throughout the follow-up period (post-prandial C peptide at 18 months: 0.63 nmol/l). It is concluded that residual insulin secretion is one of the most effective predictive factors of remission when type I diabetes is first diagnosed and remains stable for the first 18 months of the disease in patients who show a remission.

Topics: Adolescent; Adult; Aged; Body Weight; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Infusion Systems; Male; Middle Aged; Remission, Spontaneous; Time Factors

Topics: Adolescent; C-Peptide; Child; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; HLA Antigens; Humans; Remission, Spontaneous

To examine the natural course of insulin action in Type I diabetes, we followed 15 patients prospectively for one year after the diagnosis of diabetes and also performed a cross-sectional study of 53 additional patients who had had diabetes for 2 to 32 years. Two weeks after diagnosis, the rate of glucose uptake during hyperinsulinemia, a measure of insulin action, was 32 percent lower in the patients with diabetes than in 30 matched normal subjects (P less than 0.01), but it rose to normal during the subsequent three months. At three months after diagnosis, 9 of 21 patients (43 percent) were in clinical remission and did not require insulin therapy. In these patients, insulin action was 40 percent greater (P less than 0.002) than in the patients who continued to need insulin treatment. Fasting plasma C-peptide levels were slightly but not significantly higher in the patients who had a remission than in the other patients. In patients who had had diabetes for one year or more, insulin action was also reduced by an average of 40 percent (although there was considerable variation between patients), and it was inversely related to glycemic control and relative body weight. Thus, in patients with newly diagnosed Type I diabetes, a transient normalization of insulin action may occur after an initial reduction, along with a partial recovery of endogenous insulin secretion, and these events may contribute to the development of a clinical remission ("honeymoon" period). A majority of patients with diabetes of long duration are characterized by varying degrees of insulin resistance.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Prospective Studies; Remission, Spontaneous

Persistent hyperinsulinism in the newborn may warrant surgical intervention to prevent neurologic sequelae. Subtotal pancreatectomy may not be adequate, necessitating near-total pancreatectomy with subsequent development of diabetes mellitus. We report an infant with hyperinsulinemic hypoglycemia who underwent near-total pancreatectomy. The postoperative period was characterized by insulin-dependency and extreme insulin sensitivity. Clinical follow-up and C-peptide determinations showed a return of insulin secretory capacity permitting the discontinuation of insulin therapy after five months. This experience reaffirms the potential for a favorable outcome after near-total pancreatectomy in the newborn period for severe hyperinsulinism.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Humans; Hyperinsulinism; Infant; Infant, Newborn; Insulin; Pancreatectomy; Remission, Spontaneous

Three women with insulin-dependent diabetes mellitus (IDDM) from childhood and early development of diabetic retinopathy are described. Insulin requirement was reduced to 5-12 IU daily in all three after relatively uncomplicated births and all had very brittle diabetes on this dosage. At re-examination 16-22 years after these births and after 34-42 years of IDDM, regression of retinopathy was observed in two patients, while the third had a light retinopathy at the same level as initially. Other diabetic complications were few and none of the patients had nephropathy. Pituitary examination revealed incomplete hypopituitarism in all cases, human growth hormone (HGH) being the sole common factor lacking. These findings and a review of four similar cases reported previously lend some support to the hypothesis of HGH as a possible pathogenetic co-determinant in the development of diabetic retinopathy.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Female; Humans; Hypopituitarism; Middle Aged; Pituitary Function Tests; Pituitary Hormones, Anterior; Remission, Spontaneous; Thyroid Hormones; Time Factors

We studied 178 diabetic children and adolescents diagnosed during the period 1962-79 to find out the occurrence and duration of the postinitial remission, factors favoring a remission and the prognostic value of the remission. A postinitial remission occurred in 113 children (64%) being complete in only three boys (2%). The duration ranged from one month to 4.8 years, the mean being 8.4 months. The boys had a remission more often and of longer duration than the girls. The duration of diabetes was longer in the children without remission. The children with remission had lower blood glucose, milder hyperketonemia and ketonuria, higher pH and PCO2 at onset than those without remission. Hemoglobin A1 (HbA1) during 1979 were lower in the children with a positive remission history. The children with a remission lasting more than one year had a subsequently higher glucosuria index, lower HbA1 and higher C-peptide when compared to those without remission or to those with a short remission. The remission frequency increased from 1962 to 1979. Male sex and mild metabolic derangement at onset favor a postinitial remission, which results in a persisting residual beta-cell function and better metabolic control beyond the remission.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Hemoglobin A; Humans; Infant; Insulin; Ketone Bodies; Male; Remission, Spontaneous; Time Factors

The extent and the clinical significance of residual beta cell function has been evaluated by radioimmunoassay of C-peptide in 41 diabetic children in different stages of evolution, using an arginine tolerance test. In control subjects a significant rise of C-peptide levels occurred after the infusion with arginine. In patients at the onset of the disease and in patients not in the remission stage, C-peptide levels showed no increment and basal values were significantly lower than in healthy control children. Children during the remission phase showed basal and peak values not significantly different from controls. A positive correlation was found between highest CPR levels compared to basal CPR values and to the age at onset of diabetes; a negative correlation was found between the duration of the disease and insulin requirement.

Topics: Arginine; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Islets of Langerhans; Male; Peptides; Radioimmunoassay; Remission, Spontaneous

Topics: Adolescent; Adult; C-Peptide; Child; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin Secretion; Remission, Spontaneous

C-peptide secretion was studied in eight juvenile diabetics during the remission phase of the disease. The release of C-peptide was measured after a (1) normal intravenous glucose tolerance test, (2) a double glucose tolerance test, (3) an arginine infusion, and (4) after an intravenous glucose tolerance test followed by an arginine infusion. Under all conditions the intravenous glucose load had only a minimal effect on the secretion of C-peptide, while arginine alone or after the intravenous glucose tolerance test stimulated the release of the peptide in all patients. Pretreatment with glucose did not augment the effect of arginine on C-peptide release. The results indicate that during the remission phase of juvenile-onset diabetes the endocrine pancreas does not recognize glucose as and appropriate signal for C-peptide release and cannot transform the amplifying effect of glucose into a higher hormonal secretion rate.

Topics: Adolescent; Adult; Arginine; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 1; Drug Synergism; Female; Glucose Tolerance Test; Humans; Islets of Langerhans; Male; Peptides; Remission, Spontaneous

Remission of diabetes was attempted in 12 recent acute onset ketosis-prone juvenile diabetes after short term (5 +/- 1 days) but excellent blood glucose control by the external artificial beta-cell. The comparison group comrised patients undergoing traditional treatment (n = 28). Nine (75%) persistent (over 3-14 months of duration) although partial (oral drugs required) remissions were obtained in the former group as compared to 3 (11%) in the latter group (p less than 0.05). Cases which showed remissions after insulin infusion had a plasma insulin response to IV glucagon still present before insulin infusion, and a daily urinary C-peptide excretion significantly enhanced after (p less than 0.01). Urinary C-peptide/blood glucose remained improved during the remission period. Thus, early effective treatment by means of the artificial pancreas may break the vicious circle hyperglycaemia-insulin depletion-hyperglycaemia and lead to frequent and sustained remissions of juvenile diabetes.

Topics: Acute Disease; Adolescent; Adult; C-Peptide; Diabetes Mellitus, Type 1; Humans; Insulin; Monitoring, Physiologic; Pancreas; Remission, Spontaneous; Time Factors

C-peptide can be used as a measure of endogenous insulin secretion in insulin treated diabetics with insulin antibodies. At the onset of juvenile diabetes insulin production is thought to be absent or minimal, but we have found rather high levels of C-peptide, even in ketoacidotic patients. The ketoacidosis does not mean an irreversible beta cell failure. In the postinitial remission period with stable metabolism many patients have normal or almost normal C-peptide levels and their beta cells have the capacity to respond to natural stimulation with an increased insulin secretion. For some unknown reason the metabolism becomes more labile coinciding with decreasing C-peptide values. However, even several years beyond the postinitial remission period many juvenile diabetics have some persistent beta cell function, and it has been shown that even trace remnants of beta cell function are of importance for stabilization of the metabolism. There is no reason to believe that the beta cell failure should be predetermined e.g. by genetic factors. However, little is known how to influence the progression and stop the increasing beta cell failure. Some of our results suggest that an early detection and an intensive treatment of diabetes before severe metabolic disturbances and pronounced insulin deficiency have appeared, may increase the possibility of preserving some beta cell function.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Fasting; HLA Antigens; Humans; Insulin Antibodies; Islets of Langerhans; Ketones; Peptides; Physical Exertion; Proinsulin; Remission, Spontaneous

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

Serum C-peptide, insulin-binding IgG and total insulin (IRI) were determined in 96 juvenile diabetics aged 4-21 years, with onset of diabetes at the age of 1-16 years and with 2-17 years' duration of diabetes. Thirty-four patients (35.4%) had detectable levels of C-peptide (greater than or equal to 0.04 pmol/ml). Compared to non-diabetic adults, 19 had values below the normal range, 12 showed values within the normal range (0.18-0.63 pmol/ml) and 3 rated above normal. There was a negative correlation between the fasting C-peptide concentration and the degree of ketonuria at the onset of diabetes and a positive correlation between C-peptide levels and the incidence of post-initial remission periods. Patients without detectable C-peptide had significantly higher levels of insulin antibodies than those who had detectable levels of C-peptide. The possibility of a relationship between the intensity of the initial treatment of diabetes and the preservation of the B-cell function is discussed, as well as the possibility of insulin antibodies being a cause of B-cell exhaustion.

Topics: Adolescent; Adult; Age Factors; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Humans; Insulin; Insulin Antibodies; Ketone Bodies; Peptides; Remission, Spontaneous