Natural course of remission in IDDM during 1st yr after diagnosis.

OBJECTIVE--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. RESEARCH DESIGN AND METHODS--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. RESULTS--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). CONCLUSIONS--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.     

Relationship of insulin autoantibodies to presentation and early course of IDDM in children

Insulin antibodies have been documented before (insulin autoantibodies [IAAs]) and after (insulin antibodies) insulin administration in children with new-onset insulin-dependent diabetes mellitus (IDDM). Whereas the relationship of IAA to various factors at presentation has been studied in some detail, little is known about their relationship to events during the 1st yr after diagnosis. Furthermore, the course and factors affecting insulin-antibody response to human insulin administration in children with newly diagnosed IDDM remain poorly defined. To study these questions, we measured serum glucose, pH, bicarbonate, C-peptide, and IAA at diagnosis in 84 children between 0.5 and 18 yr of age. Basal and peak C-peptide responses to Sustacal ingestion, glycosylated hemoglobin (HbA1c), and IAA were then measured in 33 of these patients at 10 days and 1, 3, 6, and 12 mo after diagnosis. At presentation, IAAs were absent (binding below the mean + 3SD of the binding of control serums) in 51 patients (61%) and present (binding above the mean + 3SD) in 33 patients (39%). Multiple regression analysis showed a significant nonlinear relationship between IAAs and both age (P less than .005) and blood glucose (P less than .05) at onset. There was a stepwise increase in median insulin-antibody binding throughout the 1st yr. This increase was most marked during the 1st mo of insulin therapy and showed a statistically significant difference between successive measurements only during this period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Race-related differences in metabolic control among adults with diabetes.

The effect of race on differences in metabolic control was examined in patients with non-insulin-dependent (NIDDM) and insulin-dependent (IDDM) diabetes mellitus. Data were collected on HbA1c, age, duration of diabetes, age at onset, family function, stress, body mass index, waist/hip ratio, total cholesterol, insulin dose, diet, and physical activity. Among those with NIDDM, black patients had significantly higher HbA1c levels than their white counterparts. This difference persisted after adjustment for covariates. Among patients with IDDM, black subjects were found to have higher HbA1c levels, body mass index, and total cholesterol levels than their white counterparts. After correction for diabetes duration, relative insulin dose, physical activity, body mass index, and cholesterol, black women had significantly higher HbA1c levels than black men, white men, or white women. We conclude that race and sex differences do affect the metabolic control of patients with diabetes mellitus.     

Randomized prospective study of self-management training with newly diagnosed diabetic children

This study was designed to evaluate the effects of a self-management training (SMT) program on metabolic control of children with insulin-dependent diabetes mellitus (IDDM) in the first 2 yr after diagnosis. After standard in-hospital diabetes education, 36 children (mean age 9.3 yr, range 3-16 yr) were randomized to conventional follow-up, conventional and supportive counseling (SC), or conventional and SMT, which emphasized use of data obtained from self-monitoring of blood glucose. SC and SMT interventions consisted of seven outpatient sessions with a medical social worker during the first 4 mo after diagnosis and booster sessions at 6 and 12 mo postdiagnosis. Groups were similar with respect to age, sex, body mass index, socioeconomic status, C-peptide, and severity of illness at diagnosis. Metabolic control, measured quarterly by glycosylated hemoglobin (HbA1), improved substantially in all three treatment groups during the first 6 mo. SMT patients had significantly lower HbA1 levels than conventional patients at 1 yr (P less than 0.01) and 2 yr (P less than 0.05) postdiagnosis. SMT patients also had lower HbA1 levels than SC patients, but this did not reach statistical significance. The lower HbA1 levels of SMT patients were not explained by severity of illness at diagnosis, or insulin dose, body mass index, and C-peptide levels at 2 yr. These results suggest that an SMT program during the first few months after diagnosis helps avoid the deterioration in metabolic control often seen in children with IDDM between 6 and 24 mo after diagnosis.     

Glycemic control and peripheral nerve conduction in children and young adults after 5-6 mo of IDDM. Wisconsin Diabetes Registry.

OBJECTIVE--A cohort of people (n = 86) was examined in the first few months after insulin-dependent diabetes mellitus (IDDM) diagnosis to evaluate the effect of hyperglycemia on nerve conduction velocities and latencies. RESEARCH DESIGN AND METHODS--Unselected cases with IDDM, who were 6-29 yr of age, were identified at diagnosis from a large, geographically defined area of southern Wisconsin. Peripheral nerve conduction was measured on a sample from this cohort. RESULTS--Peroneal nerve conduction velocity was significantly inversely related to glycosylated hemoglobin (P less than 0.05, age and height adjusted). All other nerve conduction velocities and latencies (median motor, median sensory, and sural) showed the same tendency, but the associations were not statistically significant. Twenty-four-hour urine C-peptide and duration of diabetes (3-11 mo) were not consistently related to nerve conduction parameters after controlling for age and height. CONCLUSIONS--These findings suggest that as early as 5-6 mo after diabetes diagnosis, and at a time frequently characterized by partial remission of IDDM, hyperglycemia has a role in the acute slowing of nerve conduction velocity. Other factors such as residual endogenous insulin production do not appear to influence these early changes.     

Plasma endothelin-1 and total insulin exposure in diabetes mellitus.

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relationship, and ET-1 effects on vascular wall structure are similar to the long-term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their total insulin exposure to see if plasma ET-1 might be a link between insulin exposure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight glycaemic control for 2 years in a cross-sectional design. We measured basal and glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinfold thickness, glomerular filtration rate, albumin excretion rate and standard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Type II diabetes. Patients with an albumin excretion rate >300 microg/min were excluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 normal subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in Type II diabetes (P=0.0001). In all patients with measurable plasma C-peptide, plasma ET-1 was associated with basal plasma C-peptide (r=0.5018, P<0.0001), with stimulated plasma C-peptide (r=0.5379, P<0.0001), and with total daily insulin dose (r=0.2219, P=0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily insulin dose. Our study shows that the plasma concentration of ET-1 is closely associated with insulin secretion and insulin dose in patients with diabetes. Plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Increased insulin exposure in patients with diabetes may have long-term effects on vascular wall structure through its stimulation of ET-1 expression.     

Changes in insulin resistance with long-term insulin therapy

Thirteen newly diagnosed diabetic subjects, 5 with insulin-dependent diabetes mellitus (IDDM) and 8 with non-insulin-dependent diabetes mellitus, mean age 37.1 yr (range 25-64 yr), underwent glucose-clamp studies at diagnosis of diabetes at plasma glucose 200 mg/dl. Each subject was then treated twice daily with insulin for 6 mo with improvement in glycemic control, and the glucose-clamp studies repeated. Changes in glucose uptake at an insulin infusion rate of 1.0 mU X kg-1 X min-1 varied greatly from diagnosis to 6 mo. There were significant negative correlations between change in glucose uptake and diabetes type (r = -.78, P less than .002), C-peptide secretion (r = -.66, P less than .05), and age (r = -.62, P less than .05). At an insulin infusion rate of 10 mU X kg-1 X min-1 there was improvement in glucose uptake from diagnosis to 6 mo that did not reach statistical significance. During the steady-state periods of the glucose-clamp studies at diagnosis, growth hormone (GH) rose above basal, which reached statistical significance at the higher insulin infusion rate. This increase in GH was not apparent at the time of the glucose-clamp studies after insulin therapy. Our results indicate that in the clinical situation, only patients with IDDM can expect an improvement in their sensitivity to physiologic insulin levels with long-term insulin therapy. In all subjects, improvement in glycemic control leads to abolition of GH secretion in the presence of hyperglycemia.     

Does residual insulin secretion (assessed by C-peptide concentration) affect lipid and lipoprotein levels in insulin-dependent diabetes mellitus?

1. Residual endogenous insulin secretion can be assessed by the circulating C-peptide concentration and is present in up to 15% of subjects with established insulin-dependent diabetes mellitus (IDDM). Its role in lipid metabolism in IDDM is not clearly defined. We examined the relationships between serum lipid and lipoprotein concentrations and the response of circulating C-peptide to a test meal in 205 subjects with IDDM. 2. Lipid and lipoprotein levels and glycaemic control did not differ significantly between patients with undetectable, low or high C-peptide responses. 3. High density lipoprotein (HDL) cholesterol and its subfractions were inversely related to concentrations of serum triacylglycerols (P less than 0.01-0.001), but not to C-peptide or glycated haemoglobin (HbA1) levels. Levels of HbA1 and triacylglycerols were correlated with one another (P less than 0.01). Analysis of variance revealed that differences in gender and triacylglycerol concentrations were the most important determinants of HDL and HDL2 cholesterol levels. C-peptide only exerted a weak effect on HDL2 cholesterol levels and no significant predictors of HDL3 cholesterol were found. 4. It is concluded that endogenous insulin secretion (assessed by C-peptide concentration) is relatively unimportant in modifying HDL metabolism in IDDM and that associated clinical features, in particular ambient hypertriglyceridaemia, are of greater importance.     

Prednisone treatment in newly diagnosed type I diabetic children: 1-yr follow-up

Thirty-one children suffering from type I diabetes mellitus were arranged at onset of the disease in two different groups. Group 1 was treated with oral prednisone (60 mg X m-2 X day-1 for 14 days, 30 and 15 mg X m-2 X day-1 for 7 days). Group 2 matched the control group. All patients were treated with continuous subcutaneous insulin infusion for the first 15 days of treatment, and then with two daily injections of a mixture of intermediate- and fast-acting insulin. All subjects were followed for 1 yr. Group 1 required more insulin than group 2 after 30 days (1.5 +/- 0.3 vs. 0.6 $ 0.2 U X kg-1 X day-1, P less than .001) and after 60 days (0.8 +/- 0.1 vs. 0.5 +/- 0.06 U X kg-1 X day-1, P less than .001). After 3 mo, both groups reached the lowest mean stable HbA1 level (8.4 +/- 0.4 and 8.3 +/- 0.4% group 1 and 2 respectively). Between the 2nd and 9th mo of follow-up, mean postbreakfast C-peptide concentration increased in both groups. The highest levels of fasting C-peptide were reached by group 1 after 90 days (0.77 +/- 0.32 nM) and group 2 after 60 days (0.34 +/- 0.09 nM). The largest partial remission (C-peptide 0.3 nM, insulin requirement less than 0.5 U X kg-1 X day-1 and no glycosuria) was observed in group 1 after 180 days (5 of 16 patients) and in group 2 after 60 days (5 of 15 patients).(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppressor cell activity in patients with newly diagnosed insulin-dependent diabetes mellitus: a prospective study

Suppressor cell activity (SCA) was investigated longitudinally, at the time of diagnosis and during the remission period, in 17 patients with insulin-dependent diabetes mellitus (IDDM). The suppressive effect of lymphocytes from patients was investigated after incubation with concanavalin A followed by inactivation. Suppression was measured as the ability of the lymphocytes to inhibit 3H-thymidine incorporation in concanavalin A stimulated normal donor lymphocytes. The main findings were: I. SCA was reduced, on the average, at diagnosis but normal during the remission period. II. Patients with the lowest SCA at diagnosis showed significantly lower C-peptide values during the remission period than other patients. III. No relationship was found between on the one side various tissue types and on the other SCA, C-peptide values, insulin dose, and degree of glucaemic control, neither at diagnosis nor during remission. Previous studies have pointed to the significance of immune reactions in diabetogenesis. The findings in the present study may associate SCA with the development of IDDM.     

Pattern of treatment among diabetic patients in France

Both the treatment pattern and the degree of metabolic control were estimated from a sample of 1172 French diabetic patients. The subjects were recruited from 80 medical-analysis laboratories scattered throughout the country, where they came for biologic blood sample tests. Patients had to be diagnosed as having diabetes, give consent for additional blood sampling, and fill out a short self-questionnaire. Glycosylated hemoglobin A1c (HbA1c) was centrally determined by liquid chromatography (normal range 3.5-6.3%). We found 135 patients (11.5%) who were not drug treated or treated with diet alone, 862 (73.5%) treated with oral agents, and 175 (15.0%) treated with insulin. Among the latter, 79 (6.7%) were defined as true insulin-dependent diabetes mellitus (IDDM) patients. Among patients receiving no drug or a slight dosage or oral agents, 47% were found to be in the normal range of HbA1c. On the other hand, among the patients intensively treated with oral agents or secondarily with insulin, less than half were under fair control (HbA1c less than 7.5%). These results are in agreement with previous estimates of treatment distribution derived from national drug sales data. They provide evidence regarding the particular features of diabetes in France, i.e., low prevalence of IDDM, low consumption of insulin, high consumption of oral agents. The finding of a large proportion of normal HbA1c values in non-insulin-dependent diabetic patients suggests a state of overdiagnosis linked to the use of nonspecific criteria of diagnosis in large-scale screening.     

Clinical characteristics of IDDM in Hispanics and non-Hispanic whites. Little evidence of heterogeneity by ethnicity.

OBJECTIVE--To compare the clinical characteristics of IDDM in HD and NHWD subjects in order to evaluate potential heterogeneity of IDDM by ethnicity. RESEARCH DESIGN AND METHODS--HD subjects (n = 73) and NHWD subjects (n = 97) were recruited from the Colorado IDDM Registry. The registry included individuals who were Colorado residents, less than 18 yr old at diagnosis, placed on insulin within 2 wk of diagnosis, and had diabetes not secondary to other conditions. Residual beta-cell function was measured as the 1-h C-peptide response to a Sustacal challenge. RESULTS--HD subjects were similar to NHWD subjects in insulin dose, HbA1, HLA-DR antigens, ICAs, and family history of IDDM. HD subjects were more likely to have a family history of NIDDM than NHWD subjects (11 vs. 3%, P = 0.03). HD girls had higher C-peptide levels (0.27 vs. 0.11 nm/L [0.83 vs. 0.33 ng/ml], P = 0.01), BMI (22.7 vs. 20.9 kg/m2 P = 0.04), subscapular skinfold thickness (18.9 vs. 15.0 mm, P = 0.04), and WHR (0.81 vs. 0.77, P = 0.03) than NHWD females. After controlling for diabetes duration, BMI, sex, and family history of NIDDM, residual beta-cell function was associated significantly with Hispanic ethnicity, although the term accounted for just 3% of the overall variability in C-peptide levels. CONCLUSIONS--Little evidence of heterogeneity by ethnicity of IDDM patients in the Colorado IDDM Registry was found. Ethnic differences in C-peptide levels may be related to differences in body fat distribution in females rather than heterogeneity of the disease.     

Oxidative stress parameters in type I,type II and insulin-treated type 2 diabetes mellitus; insulin treatment efficiency

BACKGROUND: Our aim was to evaluate oxidative stress parameters on three groups of diabetic patients, insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-treated type 2 diabetes mellitus (ITDM2), with similar HbA1c value and to determine if insulin's impact on these parameters was the same for IDDM and ITDM2. METHODS: This study has been conducted on 18 IDDM, 55 NIDDM, 27 ITDM2, compared to 12 healthy subjects. Plasmatic concentrations of thiobarbituric acid reactive substances (TBARS), fatty acids, total antioxidant status (TAS), alpha-tocopherol, and erythrocyte reduced glutathione (GSH) were measured as well as enzymatic activities of superoxide dismutase (SOD), and glutathione peroxidase/reductase. RESULTS: Diabetic patients have significant increase of SOD activity, of TBARS concentration (concomitant with low levels of unsaturated fatty acids) and significant decrease of GSH and alpha-tocopherol. NIDDM have significantly lower levels of GSH and higher levels of TBARS compared to IDDM. ITDM2 values are intermediate between IDDM and NIDDM but are far from reaching those of IDDM. CONCLUSION: Diabetic patients undergo an important oxidative stress that is nearly corrected for IDDM, but only partially improved for ITDM2, although length of insulin treatment and HbA1c values are similar, suggesting metabolic differences between the two types of diabetes.     

New Definition for the Partial Remission Period in Children and Adolescents With Type 1 Diabetes

OBJECTIVE

To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment.

RESEARCH DESIGN AND METHODS

A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function.

RESULTS

By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient −0.21, P < 0.001) and insulin dose (−0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose–adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P < 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg⁻¹ · 24 h⁻¹ 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months.

CONCLUSIONS

A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions.Clinically, newly diagnosed type 1 diabetes is characterized by a transient partial remission period (“honeymoon”), starting shortly after insulin treatment is initiated and during which the patient''s need for exogenous insulin treatment declines and in some cases even totally disappears, and metabolic control is near optimal. The pathogenesis of this phenomenon has been the subject of discussion (1) but is likely to be a combination of two factors: partial β-cell recovery with improved insulin secretion (2) and improvement of peripheral insulin sensitivity (3).The definition of the partial remission period has varied greatly in the past. Most authors define partial remission as an insulin requirement of ≤0.5 units · kg⁻¹ · 24 h⁻¹ (4–6). However, it is not useful to define a disease state by the treatment applied, and the insulin dose is influenced by a large number of other factors. At best, this definition is reasonable when the treatment policy is uniform, which is rarely the case, even within single centers and even less so in a multicenter international study. As an extreme consequence of this definition, a diabetic patient is considered to be in partial remission when treated with a relatively low dose of insulin. To correct for this problem, others have used the definition as an A1C close to or within the normal range (7). This definition is also influenced by the treatment, as increasing the insulin dose lowers the A1C level. Furthermore, there is an initial time delay from the time of diagnosis of 4–6 weeks before a new steady-state A1C can be achieved (8). Somewhat more relevant is to combine the two definitions, that is, an insulin requirement of ≤0.5 units · kg⁻¹ · 24 h⁻¹ in combination with A1C ≤7.5% (9,10). Others have used an even lower limit for insulin requirement such as 0.3 units · kg⁻¹ · 24 h⁻¹ (11). Combining the two parameters is better than using either one alone, but having separate limits on each variable still causes a problem with the definition because a treatment change easily influences the classification of a patient.As another possibility, Komulainen et al. (12) used a basal C-peptide level of 100 pmol/l as an index for residual β-cell function. Although fasting C-peptide alone may be relatively easy to obtain in research centers and correlates with stimulated C-peptide, it is insufficient for detecting dynamic changes in residual β-cell function. Serial measurements of stimulated C-peptide that directly reflect residual β-cell function have therefore become the standard for evaluation of endogenous insulin secretion (13), but no definitions of partial remission based on stimulated C-peptide have been proposed. Besides, determination of stimulated C-peptide is a laborious, expensive, and time-consuming process and is unpleasant for the child (the patient has no breakfast and then undergoes a 90-min study and delays the morning insulin dose). Therefore, it would be useful to have an easy clinical measure for partial remission somewhat similar to the homeostasis model assessment for insulin resistance and β-cell function (14). The objective of the current longitudinal investigation was therefore to evaluate the relation between A1C and insulin dose, which are both routinely measured in clinical practice, to create a surrogate measure of stimulated C-peptide and near-normal glycemia. Furthermore, we aimed to examine the validity and reliability of this measure.     

The peculiarities of cardial arrhythmias in patients with type 2 diabetes

The aim of the study was to clarify the pathogenetic mechanisms of arrhythmias in patients with diabetes mellitus type 2 (DM 2), and the role of diabetic factors in their onset. A comparative analysis of arrhythmias was performed in 212 cardiological patients, 114 of whom had DM 2, and 98 did not. The character of concomitant pathology was similar: the patients had primary arterial hypertension, coronary heart disease, and no myocardial infarction background. The study found that the frequency of more severe and prognostically unfavorable arrhythmias was higher in the DM 2 subgroup; these arrhythmias were associated with the compensation of carbohydrate metabolism according to the level of glycated hemoglobin (HbA(1c), immunoreactive insulin (IRI), and C-peptide. Severe metabolism decompensation (HbA(1c) > 8.5%) was more often associated with ventricular arrhythmias and low IRI and C-peptide levels, whereas relatively low (< 7.0%) HbA(1c) level was associated with supraventricular arrhythmias and elevation of IRI and C-peptide levels. Arrhythmias in DM 2 were also associated with left ventricular geometric anomalies, revealed by means of electrocardiography.     

Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study.

OBJECTIVE: We undertook this study to test whether Bacillus Calmette-Guerin (BCG) vaccine preserves beta-cell function and increases the remission rate in children with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a randomized double-blind placebo-controlled trial offered to children referred to the Barbara Davis Center for Childhood Diabetes or the Baystate Medical Center with a diagnosis of new-onset type 1 diabetes. There were 94 children aged 5-18 years who received either BCG or saline intradermally within 4 months of onset of symptoms and who were then evaluated at 3-month intervals for 2 years. The primary end point was remission, defined as insulin independence for 4 weeks. Secondary end points were C-peptide levels (fasting and in response to a mixed meal challenge), insulin dose, and HbA1c. RESULTS: Of the patients, 47 were randomized to each arm; 7 in the placebo group and 9 in the BCG group did not complete 1 year of the study and are not included in the analysis. One patient from each group achieved remission. Fasting and stimulated C-peptide levels did not differ by treatment arm but declined in both groups and were lower initially and during the entire 2-year period in younger children. Insulin requirements and HbA1c levels did not differ in the two groups. CONCLUSIONS: Vaccination with BCG at the time of onset of type 1 diabetes does not increase the remission rate or preserve beta-cell function.     

Habitual physical activity in adult IDDM patients. A study with portable motion meters.

The objective of this study was to assess the habitual physical activity of insulin-dependent diabetes mellitus (IDDM) patients on intensive insulin therapy. This case-control study consisted of 34 IDDM patients (14 on multiple injection therapy, 20 on continuous subcutaneous insulin infusion [CSII], and control subjects matched for sex, age, weight, height, body mass index, smoking behavior, and occupational status). Seven IDDM patients were studied before and after changing from multiple injection to CSII therapy. All patients were well controlled according to HbA1c. Portable motion meters were used to assess habitual physical activity during 7 consecutive days with appreciable reproducibility (coefficient of variation 1.24%) and agreement to standardized activity protocols (r = 0.96, P < 0.001). Habitual physical activity was similar in IDDM patients on injection treatment and in controls, respectively. CSII-treated patients exhibited on the average 17% less habitual physical activity than control subjects (P < 0.05). Changing from multiple injection therapy to CSII lowered habitual physical activity insignificantly in seven patients. There was no indication of decreasing physical exercise (e.g., sports) by CSII in this patient group. No correlations were found between habitual physical activity and HbA1c or body mass index, respectively. Habitual physical activity is similar in IDDM patients on multiple injection therapy and control subjects, but may decrease by CSII therapy.     

Residual beta-cell function in children with IDDM: reproducibility of testing and factors influencing insulin secretory reserve

Reproducibility of C-peptide secretion was assessed in 20 children (group 1) by their responses to two Sustacal- (a mixed liquid meal) stimulation tests performed 7-14 days apart. For the 12 C-peptide-positive children (basal C-peptide greater than or equal to 0.03 pmol/ml) there were no differences in the basal or stimulated values between tests 1 and 2. The effect of exogenous insulin on C-peptide secretion was assessed in 20 other children (group 2) by their responses to two Sustacal tests, one test without and one with soluble insulin (0.25 U/kg) injected subcutaneously before testing. Eleven children were C-peptide positive and had no differences in C-peptide response between tests 1 and 2. The results from test 1 in groups 1 and 2 were combined with those from 44 others undergoing a single Sustacal test (group 3, N = 84). There was a close correlation between basal and peak C-peptide concentrations in the 44 C-peptide-positive children (r = .88, P less than .001). Peak C-peptide concentrations correlated inversely with HbA1 (r = -.29, P less than .01), insulin dose in units per kilogram (r = -.40, P less than .001), and duration of diabetes (r = .33, P less than .001) and positively with age at onset of diabetes (r = .34, P less than .001). The C-peptide-positive children had reduced glucose response to Sustacal, lower HbA1 concentration, lower insulin requirement, later age of onset, and shorter duration of diabetes than children who were C-peptide negative.     

Metabolic and immunologic effects of insulin lispro in gestational diabetes.

OBJECTIVE: To compare the immunologic response to insulin lispro with that to regular human insulin, thereby assuring its safety for use in women with gestational diabetes, and to verify that it is effective. RESEARCH DESIGN AND METHODS: We compared the metabolic and immunologic effects of insulin lispro and regular human insulin in 42 women >18 years of age diagnosed with gestational diabetes by oral glucose tolerance testing at 14-32 weeks of gestation. Patients were randomized to receive regular human insulin or insulin lispro before consuming a test meal. Serum insulin, blood glucose, and C-peptide concentrations were measured. Throughout the remainder of gestation, patients received premeal insulin lispro or regular human insulin combined with basal insulin and performed blood glucose self-monitoring before and after each meal. Insulin antibodies and HbA1c were determined at enrollment and 6 weeks later. In addition, 10 patients received continuous intravenous insulin (4 lispro, 6 regular human insulin) and dextrose infusions intrapartum to assess placental insulin transfer. RESULTS: Anti-insulin antibody levels were similar in the two groups. Insulin lispro was not detectable in the cord blood. During a meal test, areas under the curve for glucose, insulin, and C-peptide were significantly lower in the lispro group. Mean fasting and postprandial glucose concentrations and end point HbA1c were similar in the two groups. The lispro group demonstrated fewer hypoglycemic episodes (symptoms and blood glucose concentrations <55 mg/dl). No fetal or neonatal abnormalities were noted in either treatment group. CONCLUSIONS: Insulin lispro may be considered a treatment option for women with gestational diabetes.     

Indication of intensive insulin therapy and its practice

DCCT and Kumamoto Study demonstrated that optimal glycemic control with intensive insulin therapy could delay the onset and progression of the early stages of diabetic microvascular complications in Japanese patients with noninsulin dependent diabetes as well as in patients with insulin dependent diabetes mellitus. To obtain optimal glycemic control, the prandial insulin supplements before each meal are recommended for insulin requiring patients with noninsulin dependent diabetes mellitus whose residual B cell functions are retained to some extent, whereas the combined basal at bedtime plus prandial insulin supplements are essential for the patients with noninsulin dependent diabetes mellitus whose residual B cell functions are severely exhausted as well as in the patients with insulin dependent diabetes mellitus. The glycemic threshold to prevent the onset and progression of diabetic microvascular complications in the Kumamoto Study was indicated as follows; HbA1c < 6.5%, fasting blood glucose concentration < 110 mg/dl, and 2-hour postprandial blood glucose concentration < 180 mg/dl.