The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors.

AIMS: The main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34 years). METHODS: All 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19 years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. RESULTS: After median 17 years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1 kg/m²), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p = 0.041), BMI (p = 0.012) and HbA1c (p < 0.001) were significant predictors of developing diabetic nephropathy between 9 and 17 years of diabetes. At 17 years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1 mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.05 1.12 per 1 mmHg increase) were associated with DN. CONCLUSIONS: Patients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9 years of follow-up was a risk marker for later development of diabetic nephropathy.

Changing healthcare utilization patterns in diabetes mellitus: case-control studies 1 year and 8 years after diagnosis.

AIMS: To describe healthcare utilization patterns in young and middle-aged patients with diabetes 1 year and 8 years after diagnosis and to compare with the general population at two time points, 16 years apart. METHODS: Four cohorts with disease duration of 1 year or 8 years were selected from the Diabetes Incidence Study in Sweden, which registers all incident cases of diabetes in the 15- to 34-year age group. Control subjects were selected from the population register matched by age, sex and county of residence. A postal questionnaire was sent to the 1983 and 1992 cohorts in 1991 and 1993, and to the 1999 and 2008 cohorts in 2007 and 2009. Nine hundred and thirteen patients with diabetes and 1679 control subjects responded. RESULTS: One year after diagnosis, 49% of patients with diabetes in the 1992 cohort compared with 4.2% in the 2008 cohort reported visits to departments of internal medicine and endocrinology. A similar pattern was seen 8 years after diagnosis. The use of day care was 4-5 times higher among patients with diabetes compared with control subjects. Utilization of outpatient hospital care was higher among patients with diabetes compared with control subjects, even when excluding visits to diabetes clinics. CONCLUSIONS: Excess use of health care among patients with diabetes remained 16 years after the first follow-up. Utilization patterns were stable, except for a major decrease in inpatient care 1 year after diagnosis and an increase in day care 8 years after diagnosis. Observed changes probably reflect successive reforming of diabetes care in Sweden.

Long-term detrimental consequences of the onset of type 1 diabetes on annual earnings--evidence from annual registry data in 1990-2005.

AIMS/HYPOTHESIS: Young adults in the early stages of their participation in the labour market may be particularly vulnerable to the effects of onset of a chronic disease. Our aim was to quantify the consequences of the onset of type 1 diabetes in young adults on annual earnings, using individual-level longitudinal data before and after the onset of diabetes. METHODS: The Econ-DISS database contains annual socioeconomic information for 1990-2005 from Statistics Sweden. Econ-DISS includes data for persons with diabetes onset at the age of 15-34 years between 1983 and 2005, registered in the national Diabetes Incidence Study in Sweden (DISS) database, and for controls. Considering the onset of type 1 diabetes as an unanticipated and significant life event, we compared the progression of annual earnings for 3,650 cases born between 1949 and 1970 before and after onset of diabetes with that of 14,629 controls. Possible confounders--education, participation in the labour market, sick leave and parental education--were analysed. RESULTS: We found no differences between the groups in annual earnings or participation in the labour market before onset of diabetes. After onset, persons with type 1 diabetes gradually lagged behind the controls. Their median annual earnings were lower in each year from 1995 to 2005 (p < 0.01). The difference in 2005 was euro (EUR) 1,411 (5.3%). Controlling for confounders, duration of type 1 diabetes > or = 10 years was associated with 4.2% (men) and 8.1% (women) lower average annual earnings for persons with upper secondary education only who were active in the labour market. CONCLUSION/INTERPRETATION: The onset of type 1 diabetes in young adults has long-term detrimental consequences on earnings that cannot be attributed to confounders.

Gender differences and temporal variation in the incidence of type 1 diabetes: results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983-2002.

OBJECTIVES: To establish the gender difference amongst newly diagnosed type 1 diabetic patients aged 15-34 years, considering age at diagnosis, temporal trend and seasonal variation at time of diagnosis. STUDY DESIGN: A population-based prospective study with a mean annual population at risk of 2.3 million. SETTING: All departments of medicine, endocrinology and paediatrics and primary health care units in Sweden. SUBJECTS: Incident cases of diabetes aged 15-34 years at diagnosis 1983-2002. MEASURE INSTRUMENT: Basic characteristics of patients at diagnosis were reported by the diagnosing doctor on a standardized form. Level of ascertainment was estimated at 80-90%. RESULTS: Amongst all incident cases (n = 8012), 74% was diagnosed with type 1 diabetes. The mean annual incidence rate of type 1 diabetes was 12.7/100,000, in men 16.4/100,000 and in women 8.9/100,000. The incidence of type 1 diabetes decreased slowly by increasing age but was in all age groups higher in men, yielding an overall male/female ratio of 1.8. In both genders the incidence of type 1 diabetes decreased in average of 1.0% per year. A seasonal pattern with significantly higher incidence during January-March and lower during May-July was seen in both genders. CONCLUSIONS: A clear male predominance of type 1 diabetes was seen in all ages. The temporal trend and the seasonal pattern was similar in men and women. Hence, internal factors related to the gender rather than differences in the exposure to environmental factors seem to explain the consistent male-female bias in the postpubertal risk of developing type 1 diabetes.

Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS).

AIMS/HYPOTHESIS: Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes. METHODS: The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208). RESULTS: At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5+/-1.3 vs 96.7+/-2.0 nmol/l; p<0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5+/-2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9+/-1.4 vs 90.1+/-2.4 nmol/l; p<0.0001) and at follow-up (77.1+/-2.8 nmol/l vs 87.2+/-4.5 nmol/l; p=0.048). CONCLUSIONS/INTERPRETATION: The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men.

Excess mortality in incident cases of diabetes mellitus aged 15 to 34 years at diagnosis: a population-based study (DISS) in Sweden.

AIMS/HYPOTHESIS: The objective of the study was to analyse the mortality, survival and cause of death patterns in incident cases of diabetes in the 15-34-year age group that were reported to the nationwide prospective Diabetes Incidence Study in Sweden (DISS). MATERIALS AND METHODS: During the study period 1983-1999, 6,771 incident cases were reported. Identification of deaths was made by linking the records to the nationwide Cause of Death Register. RESULTS: With an average follow-up of 8.5 years, resulting in 59,231 person-years, 159 deaths were identified. Diabetes was reported as the underlying cause of death in 51 patients (32%), and as a contributing cause of death in another 42 patients (26%). The standardised mortality ratio (SMR) was significantly elevated (RR=2.4; 95% CI: 2.0-2.8). The SMR was higher for patients classified by the reporting physician as having type 2 diabetes at diagnosis than for those classified as type 1 diabetic (2.9 and 1.8, respectively). Survival analysis showed significant differences in survival curves between males and females (p=0.0003) as well as between cases with different types of diabetes (p=0.005). This pattern was also reflected in the Cox regression model showing significantly increased hazard for males vs females (p=0.0002), and for type 2 vs type 1 (p=0.015) when controlling for age. CONCLUSIONS/INTERPRETATION: This study shows a two-fold excess mortality in patients with type 1 diabetes and a three-fold excess mortality in patients with type 2 diabetes. Thus, despite advances in treatment, diabetes still carries an increased mortality in young adults, even in a country with a good economic and educational patient status and easy access to health care.

Hyperproinsulinemia segregates young adult patients with newly diagnosed autoimmune (type 1) and non-autoimmune (type 2) diabetes.

OBJECTIVE: To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. MATERIAL AND METHODS: Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. RESULTS: Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001). CONCLUSIONS: Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.

Increased risk of diabetes among relatives of female insulin-treated patients diagnosed at 15-34 years of age.

AIMS: This study aimed to determine the risk of developing diabetes among relatives of patients diagnosed between 15 and 34 years of age who were treated with insulin. Our second aim was to determine whether there was a difference in risk of diabetes between relatives of male and female patients. METHODS: A questionnaire was sent to patients in the Diabetes Incidence Study in Sweden registry diagnosed between 1983 and 1993 to determine the presence of first-degree relatives with diabetes. RESULTS: In 3087 index patients treated with insulin, 17.8% (95% confidence interval 16.5, 19.2) had a first-degree relative (excluding offspring) treated with insulin, the frequency being higher in female (19.8%) than in male (16.5%, P = 0.018) patients. A total of 10.7% had a parent treated with insulin. The prevalence of insulin-treated diabetes was higher among parents of female (12.5%) than of male (9.5%), insulin-treated index patients (P = 0.0068). A similar difference was observed using life table analysis (P = 0.0025), which also showed that the risk by 63 years of age was 7.6% for parents of female and 4.9% for parents of male insulin-treated index patients. In insulin-treated index patients, 8.4% had a sibling with insulin-treated diabetes. CONCLUSIONS: We conclude that the risk for relatives of women with insulin-treated diabetes was higher than for relatives of insulin-treated male patients. We suggest that greater genetic susceptibility is required for females compared with males in the 15-34 age group in order to develop diabetes and hence females might carry more diabetes genes since more of their relatives also develop diabetes.

Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes.

AIM: To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM). METHODS: In Sweden, 362 patients (15-34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA(1c) and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose 12 months. Among patients with antibodies (ab(+)), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20-24.9 kg/m(2)) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab(+) remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions. CONCLUSION: In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

OBJECTIVES: To establish the prevalence of remaining beta-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. DESIGN: Population-based cohort study. SETTING: Nationwide from all Departments of Medicine and Endocrinology in Sweden. SUBJECTS: A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. MAIN OUTCOME MEASURE: Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved beta-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies - were measured. RESULTS: Amongst 269 islet antibody positives (ab+) at diagnosis, preserved beta-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining beta-cell function. Amongst the 241 patients without detectable beta-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. CONCLUSIONS: Sixteen per cent of patients with autoimmune type 1 diabetes had remaining beta-cell function 8 years after diagnosis whereas 5.8% with beta-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.

Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS).

OBJECTIVE: To study trends in body mass index (BMI) at diagnosis of diabetes in all young Swedish adults in the age range of 15-34 years registered in a nation-based registry. DESIGN: The BMI was assessed at diagnosis in diabetic patients 15-34 years of age at diagnosis, for a period of 17 years (1983-1999). Islet cell antibodies (ICA) were measured during three periods (1987-1988, 1992-1993 and 1998-1999). SETTING: A nationwide study (Diabetes Incidence Study in Sweden). SUBJECTS: A total of 4727 type 1 and 1083 type 2 diabetic patients. MAIN OUTCOME MEASURES: Incidence-year specific BMI adjusted for age, gender and time of diagnosis (month). RESULTS: Body mass index at diagnosis increased significantly both in type 1 (21.4 +/- 3.6 to 22.5 +/- 4.0; P < 0.0001) and in type 2 (27.4 +/- 6.8 to 32.0 +/- 6.0; P < 0.0001) diabetic patients, also when adjusted for age, gender and month of diagnosis. A similar significant increase in BMI was found in type 1 diabetic patients and in type 2 diabetic patients in the periods 1987-1988, 1992-1993 and 1998-1999; years when ICA were assessed and considered in the classification of diabetes. Despite this increase in BMI, there was no increase in the incidence of diabetes in young-adult people in Sweden. CONCLUSION: Body mass index at diagnosis of diabetes in subjects 15-34 years of age has substantially increased during 1983-1999 in Sweden when adjusted for age, gender and month of diagnosis.

The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998.

AIMS/HYPOTHESIS: To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998. METHODS: Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers. RESULTS: Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods ( p=0.63), but time changes among the 3-year age groups differed ( p<0.001). In females the incidence between the periods varied ( p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ ( p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 ( p<0.001) (15.0 and 12.5 years in males; 11.9 and 10.4 in females, respectively). CONCLUSION/INTERPRETATION: During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.

Molecular and crystal structures of N-aryl-beta-D-glycopyranosylamines from mannose and galactose.

The molecular and crystal structures of 12 N-aryl-beta-D-glycopyranosylamines have been determined by X-ray crystallography. Six of these are mannose derivatives, the N-p-bromophenyl (1), N-p-tolyl (2), N-m-chlorophenyl (3), N-p-methoxyphenyl (4), N-o-chlorophenyl (5), and N-o-tolyl (6) derivatives that are formed by reaction with the corresponding substituted anilines. The remaining six are galactose derivatives, the N-phenyl (7), N-p-chlorophenyl (8), N-p-bromophenyl (9), N-p-iodophenyl (10), N-p-nitrophenyl (11) and N-p-tolyl (12), derivatives prepared similarly. Compounds 1-3 assume the same packing arrangement. Compounds 4, 5, and 6 assume unique packing arrangements, although that assumed by 4 is closely related to that assumed by 1-3. Compounds 7-11 assume the same packing arrangement; that assumed by 12 is closely related to that assumed by 7-11. That the same packing arrangements can be maintained in spite of substantial changes in the electronic and steric nature of the substituent on the aryl ring reflects the strength of the hydrogen bond network connecting the monosaccharide portions of the molecules in the solid state. A hydrogen bonding motif found in all six mannose structures is a mutual interaction between translationally related molecules involving O-3-H...O-5 and O-6-H...O-4 hydrogen bonds. The recurrence of this motif throughout this group of mannosylamines suggests that it is an especially favorable interaction that might be expected to occur also in related macromolecular systems.

Molecular and crystal structures of N-arylglycopyranosylamines formed by reaction between sulfanilamide and D-ribose, D-arabinose and D-mannose.

The X-ray crystal structures of three monosaccharide derivatives prepared by the reaction of sulfanilamide with D-ribose, D-arabinose, and D-mannose have been determined. The derivatives are N-(p-sulfamoylphenyl)-alpha-D-ribopyranosylamine (1), N-(p-sulfamoylphenyl)-alpha-D-arabinopyranosylamine (2), and N-(p-sulfamoylphenyl)-beta-D-mannopyranosylamine monohydrate (3). The monosaccharide ring of 1 and 2 has the 1C4 conformation, stabilized in 1 by an intramolecular hydrogen bond from 0-2 to 0-4. Compound 3 has the 4C1 conformation at the monosaccharide ring and the gt conformation at the C-6-O-6 side chain. Occupancy of the water molecule in the crystal of 3 actually examined was 22%. The degree of interaction between sulfamoyl groups and monosaccharide moieties varies from structure to structure. The packing arrangement of 2 involves hydrogen bonding between sulfamoyl groups and monosaccharide hydroxyl groups, but interactions of this type are fewer in 1, and in 3 the hydrogen bonds are either strictly between monosaccharide hydroxyl groups or strictly between sulfamoyl groups. Pairs of hydrogen bonds (two-point contacts) link neighboring molecules in all three structures, between screw-axially related molecules in 1 and 2 and between translationally related molecules in 3. The contact in 3 defined by the O-3-H...O-5 and O-6-H...O-4 hydrogen bonds is found in several other N-aryl-beta-D-mannopyranosylamine crystal structures and is apparently an especially favorable mode of intermolecular interaction in these compounds.

Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults: a nationwide study.

OBJECTIVE: To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS: The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR]2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients; however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS: Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.

Increased mortality in diabetes during the first 10 years of the disease. A population-based study (DISS) in Swedish adults 15-34 years old at diagnosis.

OBJECTIVES: To study, prospectively, in young adult patients, the mortality during the first years after the diagnosis of diabetes. DESIGN: The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases aged 15-34 years. During a 10-year period all deaths were identified by record linkage to the national Cause of Death Registry. SUBJECTS: During the period, 4097 new cases were registered and classified as type 1 diabetes (73%), type 2 (16%), secondary (2%) and unclassified (9%). The median follow-up was 5 years (21 001 person-years). MAIN OUTCOME MEASURES: Calculation of the standardized mortality ratio (SMR) and 95% confidence interval (CI). Evaluation of all deceased by scrutiny of clinical records, death certificates and autopsy protocols. RESULTS: Fifty-eight patients died, corresponding to an SMR of 3.5 (CI=2.7-4.5), which increased from 1.5 at 15-19 years to 4.1 at 30-34 years. SMR was 2.7 in primary diabetes: 2.3 (1.6-3.3) in type 1 and 4.1 (2.6-6.7) in type 2. In secondary diabetes, alcohol-associated pancreatitis a common cause, SMR was 32 (CI=24-45). Evidence of alcohol or drug misuse, mental dysfunction or suicide was found in 40 of all 58 deceased cases. Less often, hypoglycaemia (n=7) or hyperglycaemia-ketoacidosis (n=11) was present at death. Unexplained 'dead in bed' was found once. CONCLUSIONS: In the investigated population-based cohort the early mortality was about threefold increased. Hypoglycaemia and ketoacidosis per se played a relatively small role compared with a heavy impact from social and mental dysfunction, and from careless use of alcohol or drugs.

Combinations of beta cell specific autoantibodies at diagnosis of diabetes in young adults reflects different courses of beta cell damage.

To explore the natural course of beta cell function in recent onset diabetes, a subgroup (n=157) of all incident cases (n=879) 15-34 years old, 1992-1993 in Sweden, and with positivity for at least one autoantibody of islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A) were followed prospectively for the first four years with annual analysis of C-peptide. The aim was to relate the course of beta cell function, measured as C-peptide, in early diabetes with the presence of different islet autoantibodies at diagnosis. We found that patients positive for ICA alone (n=11) had significantly higher C-peptide levels both at diagnosis and during the first three years compared with the other patients (n=146; p=0.022, p<0.001, p=0.004 and p=0.0022). Patients positive for GADA alone or in combination with other antibodies (n=125) had significantly lower C-peptide during the first three years after diagnosis compared with the other patients (n=32, p<0.001, p=0.0011 and p=0.0136). Patients with two or three autoantibodies had C-peptide levels similar to levels found in patients positive only for GADA. However, after four years, there were no significant differences between any of the groups of different autoantibody combinations. At diagnosis, 55% (86/157) of the patients had C-peptide levels above the lower normal range of 0.25 nmol/l, but the frequency of patients with beta cell function above this level decreased after two years to 41% (65/157; p=0.035) and after four years to 22% (35/157; p=0.0041). It is concluded that young adult diabetic patients positive only for ICA at diagnosis have a better preserved beta cell function with higher levels of C-peptide during the first three years compared with patients positive for GADA alone or in combinations with other autoantibodies.

Glutamic acid decarboxylase antibodies (GADA) is the most important factor for prediction of insulin therapy within 3 years in young adult diabetic patients not classified as Type 1 diabetes on clinical grounds.

BACKGROUND: Differentiation between Type 1 and Type 2 diabetes in adults is difficult at diagnosis. In this study we tested the hypothesis that autoantibodies at diagnosis are predictive for insulin treatment within 3 years in patients initially not classified as Type 1 diabetes. METHODS: In a nationwide population-based study, blood samples were obtained from 764 patients, all diagnosed with diabetes during a 2-year period. At diagnosis, 583 (76%) were classified as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classified. RESULTS: Among patients not classified as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassified patients were positive for islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A). These patients (n=94) had lower body mass index (BMI) (p<0.001) and lower C-peptide (p<0.001) compared to the autoantibody negative patients (n=87). Compared to clinically classified Type 1 diabetes patients positive for autoantibodies (n=477), they have higher BMI (p<0.001), higher C-peptide (p<0.001) and the same levels of ICA, GADA and IA-2A. After 3 years, 93% of autoantibody positive patients initially not classified as Type 1 were on insulin. When ICA, GADA, IA-2A, BMI and C-peptide were tested in a multiple logistic regression, only GADA was significant for insulin treatment within 3 years (OR=18.8; 95% CI 1.8-191) in patients treated with diet or oral drugs at diagnosis. CONCLUSIONS: A correct classification is difficult in adult diabetic patients. The presence of pancreatic autoantibodies, especially GADA, at diagnosis of diabetes are highly predictive for insulin therapy within 3 years from diagnosis.

Excess costs of medical care 1 and 8 years after diagnosis of diabetes: estimates from young and middle-aged incidence cohorts in Sweden.

To analyze the excess costs of medical care during the first decade after diabetes diagnosis, we surveyed two national incidence cohorts who contracted diabetes at age of 15-34 years and matched control groups from the general population of Sweden. Ninety percent of the diabetic subjects were on insulin treatment. Data on healthcare utilization and use of glucose lowering drugs and medical devices were collected via a questionnaire mailed to a recent cohort 1 year after diagnosis and a previously registered cohort 8 years after diagnosis. Costing was based on average national costs of hospital inpatient and out-patient care, an original study of daycare costs, and sales prices of the National Corporation of Swedish Pharmacies. One year after diabetes diagnosis, the annual excess costs of care were US$4743 among men and US$4976 among women (1997 prices). Hospital inpatient care accounted for more than 50% of the excess costs. Eight years after diagnosis, the excess costs were US$2010 among men and US$2734 among women. The higher costs for women were mainly related to hospital out-patient care, but also to more intensive self-monitoring. We conclude that diabetes in young and middle-aged people is a major economic challenge even before significant complications may have developed.

Schiff bases or glycosylamines: crystal and molecular structures of four derivatives of D-mannose.

Crystal and molecular structures of four derivatives of D-mannose are described. Each could exist as either an open-chain Schiff base or as a glycosylamine in the solid state. The derivative formed upon reaction of D-mannose with hydroxylamine is an open-chain oxime, but those formed upon reaction with semicarbazide, aniline, and p-chloroaniline are glycosylamines. The oxime, which crystallizes as the syn-(E) isomer, has a fully extended carbon chain. The glycosylamines are all beta-pyranoses. The packing arrangement of the oxime involves 'head-to-tail' hydrogen bonding. The semicarbazide derivative, which crystallizes as a dihydrate, features a hydrogen-bonded intramolecular bridge formed by the two water molecules and linking O-6 to the carbonyl oxygen atom. The packing arrangements of the aniline and p-chloroaniline derivatives differ from each other but are nevertheless closely related by similar hydrogen-bonding interactions.