The Diabetes Incidence Study in Sweden (DISS) registers diabetes in young adults aged 15-34 years... more The Diabetes Incidence Study in Sweden (DISS) registers diabetes in young adults aged 15-34 years in Sweden. This thesis aims to validate the ascertainment, methods in the classification of diabetes, and putative etiological factors such as family background, psychological stress, and BMI, that may affect the incidence of diabetes in young adults, in the DISS registry. The capture-recapture method was used in the evaluation of ascertainment, whereas C-peptide and islet antibodies (islet cell antibodies ?ICA? and glutamic acid decarboxylase antibodies ?GADA?) were used in the classification of diabetes. In a case-control study 1992-1993, autoimmune Type 1 diabetic patients were compared with controls. Body mass index (BMI) was calculated from weight and height in the registration forms 1983-1999. Level of ascertainment in the DISS registry was 0.86 for Type 1 diabetes. Clinical characteristics at diagnosis or C-peptide values 2.5-3 years after diagnosis did not clarify whether the ty...
In the present study we have investigated glucose metabolism, insulin secretion and lipid-and lip... more In the present study we have investigated glucose metabolism, insulin secretion and lipid-and lipoprotein profiles in first degree relatives to subjects with type 2 diabetes mellitus and in subjects without a family history of diabetes. The aim of the study was to investigate whether the lipid disturbance seen in type 2 diabetes mellitus could also be revealed in subjects with a family history of diabetes but with normal glucose tolerance. A random sample of 70 (32 men) first degree relatives to subjects with type 2 diabetes and 32 (17 men) subjects without a family history of diabetes were studied. An oral glucose tolerance test (OGTT) was performed and lipid-and lipoproteins were analyzed in all subjects. A glucose infusion test was performed in a sub-sample (n=20) of first degree relatives with a normal OGTT in order to measure the early insulin response in relation to plasma lipid levels. Four subjects with a family history of diabetes were diagnosed with diabetes and another ei...
All newly diagnosed cases of diabetes mellitus aged 15–34 years in Sweden, where the population i... more All newly diagnosed cases of diabetes mellitus aged 15–34 years in Sweden, where the population in this age interval is about 2.3 million, were registered on standardized forms. During 1983, the first year of the study, there were 311 males and 161 females, excluding 280 with gestational diabetes. The annual incidence of diabetes was 26.2 per 100000 in males and 14.2 in females. The respective figures for type I were 18.5 and 10.1, and for type II 5.7 and 2.9. The incidence of type I diabetes was similar for the four age groups (15–19, 20–24, 25–29, 30–34 years), while for type II it was highest in the oldest group. Types I and II, but not the sexes, differed as regards the cumulative distribution curves of the maximum blood glucose concentration during the first two weeks after diagnosis. The present incidence of diabetes in Sweden is higher, particularly in males than the rates for similar age groups in Oslo (1925–64) and Denmark (1970–77).
OBJECTIVES: Gastroparesis is a well-known complication of diabetes mellitus, both in symptomatic ... more OBJECTIVES: Gastroparesis is a well-known complication of diabetes mellitus, both in symptomatic and asymptomatic patients. Esophageal dysmotility has also been described, but is not as well-characterized. The etiology and effect of these complications need to be clarified. The aim of the present study was to evaluate esophageal and gastric motility, complications, gastrointestinal symptoms, and plasma biomarkers in a cross-sectional study comprising patients with diabetes mellitus. METHODS: Patients with diabetes were consecutively asked to participate, and eventually 84 volunteers were included in the study. Esophageal manometry and the gastric emptying test were performed in all patients. Type of diabetes, symptoms, diabetic complications, body mass index (BMI), and biomarkers were recorded. Patients were interviewed about gastrointestinal symptoms. RESULTS: Esophageal dysmotility was present in 63% of patients and gastroparesis in 13% of patients. There was no difference in dysmotility between patients with type 1 and type 2 diabetes or between genders. Gastrointestinal symptoms did not correlate to objective findings. Age correlated negatively with gastric emptying rate (p = 0.004). Patients with esophageal dysmotility had longer duration of diabetes compared to those without dysmotility (p = 0.043). In logistic regression analysis, retinopathy was strongly associated with esophageal dysmotility, independent of duration (p = 0.003). CONCLUSIONS: Esophageal dysmotility is more common than gastroparesis in diabetes mellitus independent of gender, symptoms, and type of diabetes. There is a strong association between retinopathy and esophageal dysmotility.
Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the... more Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS).
Increased mortality in diabetes during the ®rst 10 years of the disease. A population-based study... more Increased mortality in diabetes during the ®rst 10 years of the disease. A population-based study (DISS) in Swedish adults 15±34 years old at diagnosis. J Intern Med 2001; 249: 263±270. Objectives. To study, prospectively, in young adult patients, the mortality during the ®rst 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 identi®ed by record linkage to the national Cause of Death Registry. Subjects. During the period, 4097 new cases were registered and classi®ed as type 1 diabetes (73%), type 2 (16%), secondary (2%) and unclassi®ed (9%). The median follow-up was 5 years (21 001 personyears). Main outcome measures. Calculation of the standardized mortality ratio (SMR) and 95% con®dence interval (CI). Evaluation of all deceased by scrutiny of clinical records, death certi®cates 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.
The Journal of Clinical Endocrinology & Metabolism, 2000
This study presents a 2-yr follow-up of 281 patients, aged 15–34 yr, diagnosed with diabetes betw... more This study presents a 2-yr follow-up of 281 patients, aged 15–34 yr, diagnosed with diabetes between 1992 and 1993. At diagnosis, 224 (80%) patients were positive for at least one of the following autoantibodies: islet cell antibodies (ICAs), glutamic acid decarboxylase antibodies (GADAs), or tyrosine phosphatase antibodies (IA-2As); the remaining 57 (20%) patients were negative for all three autoantibodies. At diagnosis, C-peptide levels were lower (0.27; 0.16–0.40 nmol/L) in autoantibody-positive patients compared with autoantibody-negative patients (0.51; 0.28–0.78 nmol/L; P < 0.001). After 2 yr, C-peptide levels had decreased significantly in patients with autoimmune diabetes (0.20; 0.10–0.37 nmol/L; P = 0.0018), but not in autoantibody-negative patients. In patients with autoimmune diabetes, a low initial level of C-peptide (odds ratio, 2.6; 95% confidence interval, 1.7–4.0) and a high level of GADAs (odds ratio, 2.5; 95% confidence interval, 1.1–5.7) were risk factors for a...
This study analyses data from two nationwide prospective diabetes registries now covering about 3... more This study analyses data from two nationwide prospective diabetes registries now covering about 3400 cases from 19 million person-years of follow-up in the age group 0-34 years. The risk of developing insulin-dependent diabetes mellitus (IDDM) per 100,000 individuals before 15 years was 386 (95% confidence intervals (CI): 362-410) for boys and 391 (95% CI: 367-415) for girls and by 35 years 701 (95% CI: 671-731) for men and 562 (95% CI: 534-690) for women. The incidence rate showed a maximum for both boys and girls in early puberty. After pubertal years a sharp increase in the male to female incidence ratio of IDDM was notable. At 10-14 years it was 0.94, at 15-19 years 1.59 and at 20-24 years 2.08. A Cox regression model was used to analyse the effects on age at onset of sex, population density and climatological factors as measured by north-south area of residence and season at onset. The effect of sex was confirmed (P less than 0.001). A significant effect (P = 0.004) of season was shown when the four seasons were classified according to a four stage scale related to mean temperature. When dividing Sweden into 11 regions according to north-south gradient (Latitude 55 degrees, 56 degrees, 57 degrees, ..., 65 degrees) a significant effect (P = 0.038) was also found. However, no effects of population density or living near the coast versus in the interior were found. It is concluded that a large proportion of the young are at risk of developing this chronic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of diabetes mellitus in Sweden in the 15-34 year age group was prospectively studie... more The incidence of diabetes mellitus in Sweden in the 15-34 year age group was prospectively studied on a nationwide basis, beginning 1 January 1983. A total of 1,214 male and 720 female cases of newly-diagnosed (excluding gestational) diabetes were reported over a 5-year period. This corresponds to an incidence of 20.5 per 100,000/year in male subjects and 12.7 per 100,000/year in female subjects. Most cases were classified as Type 1 (insulin-dependent) diabetes, with an incidence of 15.9 in males and 8.6 in females. The incidence of Type 1 diabetes decreased gradually with age, while the incidence of Type 2 (non-insulin-dependent) diabetes increased. A male predominance was found in all age groups, with a male-to-female ratio of 1.8:1 for Type 1 diabetes and 1.3:1 for Type 2 diabetes. Maximum blood glucose concentration at diagnosis was significantly higher in males than in females in both Type 1 and Type 2 diabetic subjects. In contrast, the percent desirable weight was significantly higher in females, both in Type 1 and Type 2 diabetic subjects. The difference in diabetes incidence therefore cannot be attributed to any methodological error. The present finding of a marked male predominance after puberty in Type i diabetes in an ethnically quite homogeneous population supports the hypothesis that environmental risk factors and lifestyle are important for the development of the disease.
All newly diagnosed diabetic patients in Sweden aged 15-34 years have been registered since 1983.... more All newly diagnosed diabetic patients in Sweden aged 15-34 years have been registered since 1983. In this study the clinical characteristics initially and after 2.5-3 years were evaluated by a questionnaire to the patient&#39;s physician and by non-fasting C-peptide. The study comprised patients registered 1983-84, and for 281 patients (37%), complete information was obtained. At diagnosis 75% were classified as Type 1, 19% as Type 2, and 6% as secondary diabetes or as uncertain by their physician. Twenty patients (7.1%) were reported to have ketoacidosis. Seventy-five percent were treated with insulin, 7% with oral hypoglycaemic agents (OHG), and 18% with diet alone. At follow-up 71% were classified as Type 1, 21% as Type 2, and 8% as secondary or uncertain while treatment was 82% insulin, 8% OHG, and 9% diet. During the follow-up period 42% of the initially non-insulin-treated patients were put on insulin whereas only a few stopped insulin treatment. Patients treated with diet or OHG at follow-up were older, had higher percent desirable weight, and lower blood glucose at diagnosis than patients treated with insulin. All except one patient had measurable random C-peptide at follow-up and mean values were for patients treated with insulin 0.55, OHG 1.41 and diet alone 1.29 nmol l-1. Random blood glucose results were similar. In conclusion the majority of newly diagnosed patients in the age group 15-34 years have the characteristics of Type 1 diabetes and Type 2 diabetes is rare before 25-30 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to evaluate the degree of ascertainment in a nationwide prospective reg... more The aim of this study was to evaluate the degree of ascertainment in a nationwide prospective registration of incident cases of diabetes mellitus in the age group 15-34 years (The Diabetes Incidence Study in Sweden (DISS)). Incident cases of diabetes mellitus in DISS during a five year period were compared with inpatients, with the diagnosis of diabetes mellitus, registered in a routine computer-based administrative register. The Patient Administrative System-Inpatient Care (PAS-IC). To clarify this issue the two-sample capture-recapture phenomena was employed in the two southernmost counties in Sweden, Malmöhus and Kristianstad, covering 9.2% of the total of 2.3 million people aged 15-34 years in Sweden. The results showed that the ascertainment level in DISS was 0.86 for insulin dependent diabetes mellitus (IDDM). Hence, the DISS registry is a valid tool to monitor the incidence of IDDM in young (15-34 years) adult subjects.
OBJECTIVE: To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA)... more OBJECTIVE: To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes. RESEARCH DESIGN AND METHODS: The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay. RESULTS: Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of t...
OBJECTIVE—To elucidate whether family characteristics and stressful life events were associated w... more 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 dete...
Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GAD65Ab) are often presen... more Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GAD65Ab) are often present at diagnosis of insulin dependent diabetes mellitus (type I diabetes) and are supposed to decline in level and frequency during the first years of disease. We have analysed ICA and GAD65Ab at onset and after one year in 395 population based randomly selected 15-34 year old patients newly diagnosed with diabetes mellitus, to study how these autoantibodies persist, disappear and appear and their relation to C-peptide levels. Of the 395 samples 212 (54%) were positive for ICA, 250 (63%) were positive for GAD65Ab and 170 (43%) were positive for both. At follow up after one year, 27/183 (15%) of the ICA negative patients and 25/145 (17%) of the GAD65Ab negative patients had converted to positivity. Among the 103 patients negative for both ICA and GAD65Ab, 16 turned positive for one or both antibodies after one year. Patients converting to positivity for one or the other antibody after one year, had lower C-peptide levels after one year than patients who initially were and remained negative, supporting the hypothesis that these patients have a genuine type I diabetes. In conclusion, newly diagnosed patients may be negative for autoantibodies at diagnosis but develop these antibodies later on during the disease.
To explore the natural course of beta cell function in recent onset diabetes, a subgroup (n=157) ... more 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&amp;amp;lt;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&amp;amp;lt;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.
Background Differentiation between Type 1 and Type 2 diabetes in adults is dif®cult at diagnosis.... more Background Differentiation between Type 1 and Type 2 diabetes in adults is dif®cult 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 classi®ed 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 classi®ed as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classi®ed. Results Among patients not classi®ed as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassi®ed 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 classi®ed 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 classi®ed 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 signi®cant 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 classi®cation is dif®cult 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.
The Diabetes Incidence Study in Sweden (DISS) registers diabetes in young adults aged 15-34 years... more The Diabetes Incidence Study in Sweden (DISS) registers diabetes in young adults aged 15-34 years in Sweden. This thesis aims to validate the ascertainment, methods in the classification of diabetes, and putative etiological factors such as family background, psychological stress, and BMI, that may affect the incidence of diabetes in young adults, in the DISS registry. The capture-recapture method was used in the evaluation of ascertainment, whereas C-peptide and islet antibodies (islet cell antibodies ?ICA? and glutamic acid decarboxylase antibodies ?GADA?) were used in the classification of diabetes. In a case-control study 1992-1993, autoimmune Type 1 diabetic patients were compared with controls. Body mass index (BMI) was calculated from weight and height in the registration forms 1983-1999. Level of ascertainment in the DISS registry was 0.86 for Type 1 diabetes. Clinical characteristics at diagnosis or C-peptide values 2.5-3 years after diagnosis did not clarify whether the ty...
In the present study we have investigated glucose metabolism, insulin secretion and lipid-and lip... more In the present study we have investigated glucose metabolism, insulin secretion and lipid-and lipoprotein profiles in first degree relatives to subjects with type 2 diabetes mellitus and in subjects without a family history of diabetes. The aim of the study was to investigate whether the lipid disturbance seen in type 2 diabetes mellitus could also be revealed in subjects with a family history of diabetes but with normal glucose tolerance. A random sample of 70 (32 men) first degree relatives to subjects with type 2 diabetes and 32 (17 men) subjects without a family history of diabetes were studied. An oral glucose tolerance test (OGTT) was performed and lipid-and lipoproteins were analyzed in all subjects. A glucose infusion test was performed in a sub-sample (n=20) of first degree relatives with a normal OGTT in order to measure the early insulin response in relation to plasma lipid levels. Four subjects with a family history of diabetes were diagnosed with diabetes and another ei...
All newly diagnosed cases of diabetes mellitus aged 15–34 years in Sweden, where the population i... more All newly diagnosed cases of diabetes mellitus aged 15–34 years in Sweden, where the population in this age interval is about 2.3 million, were registered on standardized forms. During 1983, the first year of the study, there were 311 males and 161 females, excluding 280 with gestational diabetes. The annual incidence of diabetes was 26.2 per 100000 in males and 14.2 in females. The respective figures for type I were 18.5 and 10.1, and for type II 5.7 and 2.9. The incidence of type I diabetes was similar for the four age groups (15–19, 20–24, 25–29, 30–34 years), while for type II it was highest in the oldest group. Types I and II, but not the sexes, differed as regards the cumulative distribution curves of the maximum blood glucose concentration during the first two weeks after diagnosis. The present incidence of diabetes in Sweden is higher, particularly in males than the rates for similar age groups in Oslo (1925–64) and Denmark (1970–77).
OBJECTIVES: Gastroparesis is a well-known complication of diabetes mellitus, both in symptomatic ... more OBJECTIVES: Gastroparesis is a well-known complication of diabetes mellitus, both in symptomatic and asymptomatic patients. Esophageal dysmotility has also been described, but is not as well-characterized. The etiology and effect of these complications need to be clarified. The aim of the present study was to evaluate esophageal and gastric motility, complications, gastrointestinal symptoms, and plasma biomarkers in a cross-sectional study comprising patients with diabetes mellitus. METHODS: Patients with diabetes were consecutively asked to participate, and eventually 84 volunteers were included in the study. Esophageal manometry and the gastric emptying test were performed in all patients. Type of diabetes, symptoms, diabetic complications, body mass index (BMI), and biomarkers were recorded. Patients were interviewed about gastrointestinal symptoms. RESULTS: Esophageal dysmotility was present in 63% of patients and gastroparesis in 13% of patients. There was no difference in dysmotility between patients with type 1 and type 2 diabetes or between genders. Gastrointestinal symptoms did not correlate to objective findings. Age correlated negatively with gastric emptying rate (p = 0.004). Patients with esophageal dysmotility had longer duration of diabetes compared to those without dysmotility (p = 0.043). In logistic regression analysis, retinopathy was strongly associated with esophageal dysmotility, independent of duration (p = 0.003). CONCLUSIONS: Esophageal dysmotility is more common than gastroparesis in diabetes mellitus independent of gender, symptoms, and type of diabetes. There is a strong association between retinopathy and esophageal dysmotility.
Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the... more Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS).
Increased mortality in diabetes during the ®rst 10 years of the disease. A population-based study... more Increased mortality in diabetes during the ®rst 10 years of the disease. A population-based study (DISS) in Swedish adults 15±34 years old at diagnosis. J Intern Med 2001; 249: 263±270. Objectives. To study, prospectively, in young adult patients, the mortality during the ®rst 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 identi®ed by record linkage to the national Cause of Death Registry. Subjects. During the period, 4097 new cases were registered and classi®ed as type 1 diabetes (73%), type 2 (16%), secondary (2%) and unclassi®ed (9%). The median follow-up was 5 years (21 001 personyears). Main outcome measures. Calculation of the standardized mortality ratio (SMR) and 95% con®dence interval (CI). Evaluation of all deceased by scrutiny of clinical records, death certi®cates 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.
The Journal of Clinical Endocrinology & Metabolism, 2000
This study presents a 2-yr follow-up of 281 patients, aged 15–34 yr, diagnosed with diabetes betw... more This study presents a 2-yr follow-up of 281 patients, aged 15–34 yr, diagnosed with diabetes between 1992 and 1993. At diagnosis, 224 (80%) patients were positive for at least one of the following autoantibodies: islet cell antibodies (ICAs), glutamic acid decarboxylase antibodies (GADAs), or tyrosine phosphatase antibodies (IA-2As); the remaining 57 (20%) patients were negative for all three autoantibodies. At diagnosis, C-peptide levels were lower (0.27; 0.16–0.40 nmol/L) in autoantibody-positive patients compared with autoantibody-negative patients (0.51; 0.28–0.78 nmol/L; P < 0.001). After 2 yr, C-peptide levels had decreased significantly in patients with autoimmune diabetes (0.20; 0.10–0.37 nmol/L; P = 0.0018), but not in autoantibody-negative patients. In patients with autoimmune diabetes, a low initial level of C-peptide (odds ratio, 2.6; 95% confidence interval, 1.7–4.0) and a high level of GADAs (odds ratio, 2.5; 95% confidence interval, 1.1–5.7) were risk factors for a...
This study analyses data from two nationwide prospective diabetes registries now covering about 3... more This study analyses data from two nationwide prospective diabetes registries now covering about 3400 cases from 19 million person-years of follow-up in the age group 0-34 years. The risk of developing insulin-dependent diabetes mellitus (IDDM) per 100,000 individuals before 15 years was 386 (95% confidence intervals (CI): 362-410) for boys and 391 (95% CI: 367-415) for girls and by 35 years 701 (95% CI: 671-731) for men and 562 (95% CI: 534-690) for women. The incidence rate showed a maximum for both boys and girls in early puberty. After pubertal years a sharp increase in the male to female incidence ratio of IDDM was notable. At 10-14 years it was 0.94, at 15-19 years 1.59 and at 20-24 years 2.08. A Cox regression model was used to analyse the effects on age at onset of sex, population density and climatological factors as measured by north-south area of residence and season at onset. The effect of sex was confirmed (P less than 0.001). A significant effect (P = 0.004) of season was shown when the four seasons were classified according to a four stage scale related to mean temperature. When dividing Sweden into 11 regions according to north-south gradient (Latitude 55 degrees, 56 degrees, 57 degrees, ..., 65 degrees) a significant effect (P = 0.038) was also found. However, no effects of population density or living near the coast versus in the interior were found. It is concluded that a large proportion of the young are at risk of developing this chronic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of diabetes mellitus in Sweden in the 15-34 year age group was prospectively studie... more The incidence of diabetes mellitus in Sweden in the 15-34 year age group was prospectively studied on a nationwide basis, beginning 1 January 1983. A total of 1,214 male and 720 female cases of newly-diagnosed (excluding gestational) diabetes were reported over a 5-year period. This corresponds to an incidence of 20.5 per 100,000/year in male subjects and 12.7 per 100,000/year in female subjects. Most cases were classified as Type 1 (insulin-dependent) diabetes, with an incidence of 15.9 in males and 8.6 in females. The incidence of Type 1 diabetes decreased gradually with age, while the incidence of Type 2 (non-insulin-dependent) diabetes increased. A male predominance was found in all age groups, with a male-to-female ratio of 1.8:1 for Type 1 diabetes and 1.3:1 for Type 2 diabetes. Maximum blood glucose concentration at diagnosis was significantly higher in males than in females in both Type 1 and Type 2 diabetic subjects. In contrast, the percent desirable weight was significantly higher in females, both in Type 1 and Type 2 diabetic subjects. The difference in diabetes incidence therefore cannot be attributed to any methodological error. The present finding of a marked male predominance after puberty in Type i diabetes in an ethnically quite homogeneous population supports the hypothesis that environmental risk factors and lifestyle are important for the development of the disease.
All newly diagnosed diabetic patients in Sweden aged 15-34 years have been registered since 1983.... more All newly diagnosed diabetic patients in Sweden aged 15-34 years have been registered since 1983. In this study the clinical characteristics initially and after 2.5-3 years were evaluated by a questionnaire to the patient&#39;s physician and by non-fasting C-peptide. The study comprised patients registered 1983-84, and for 281 patients (37%), complete information was obtained. At diagnosis 75% were classified as Type 1, 19% as Type 2, and 6% as secondary diabetes or as uncertain by their physician. Twenty patients (7.1%) were reported to have ketoacidosis. Seventy-five percent were treated with insulin, 7% with oral hypoglycaemic agents (OHG), and 18% with diet alone. At follow-up 71% were classified as Type 1, 21% as Type 2, and 8% as secondary or uncertain while treatment was 82% insulin, 8% OHG, and 9% diet. During the follow-up period 42% of the initially non-insulin-treated patients were put on insulin whereas only a few stopped insulin treatment. Patients treated with diet or OHG at follow-up were older, had higher percent desirable weight, and lower blood glucose at diagnosis than patients treated with insulin. All except one patient had measurable random C-peptide at follow-up and mean values were for patients treated with insulin 0.55, OHG 1.41 and diet alone 1.29 nmol l-1. Random blood glucose results were similar. In conclusion the majority of newly diagnosed patients in the age group 15-34 years have the characteristics of Type 1 diabetes and Type 2 diabetes is rare before 25-30 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of this study was to evaluate the degree of ascertainment in a nationwide prospective reg... more The aim of this study was to evaluate the degree of ascertainment in a nationwide prospective registration of incident cases of diabetes mellitus in the age group 15-34 years (The Diabetes Incidence Study in Sweden (DISS)). Incident cases of diabetes mellitus in DISS during a five year period were compared with inpatients, with the diagnosis of diabetes mellitus, registered in a routine computer-based administrative register. The Patient Administrative System-Inpatient Care (PAS-IC). To clarify this issue the two-sample capture-recapture phenomena was employed in the two southernmost counties in Sweden, Malmöhus and Kristianstad, covering 9.2% of the total of 2.3 million people aged 15-34 years in Sweden. The results showed that the ascertainment level in DISS was 0.86 for insulin dependent diabetes mellitus (IDDM). Hence, the DISS registry is a valid tool to monitor the incidence of IDDM in young (15-34 years) adult subjects.
OBJECTIVE: To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA)... more OBJECTIVE: To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes. RESEARCH DESIGN AND METHODS: The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay. RESULTS: Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of t...
OBJECTIVE—To elucidate whether family characteristics and stressful life events were associated w... more 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 dete...
Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GAD65Ab) are often presen... more Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GAD65Ab) are often present at diagnosis of insulin dependent diabetes mellitus (type I diabetes) and are supposed to decline in level and frequency during the first years of disease. We have analysed ICA and GAD65Ab at onset and after one year in 395 population based randomly selected 15-34 year old patients newly diagnosed with diabetes mellitus, to study how these autoantibodies persist, disappear and appear and their relation to C-peptide levels. Of the 395 samples 212 (54%) were positive for ICA, 250 (63%) were positive for GAD65Ab and 170 (43%) were positive for both. At follow up after one year, 27/183 (15%) of the ICA negative patients and 25/145 (17%) of the GAD65Ab negative patients had converted to positivity. Among the 103 patients negative for both ICA and GAD65Ab, 16 turned positive for one or both antibodies after one year. Patients converting to positivity for one or the other antibody after one year, had lower C-peptide levels after one year than patients who initially were and remained negative, supporting the hypothesis that these patients have a genuine type I diabetes. In conclusion, newly diagnosed patients may be negative for autoantibodies at diagnosis but develop these antibodies later on during the disease.
To explore the natural course of beta cell function in recent onset diabetes, a subgroup (n=157) ... more 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&amp;amp;lt;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&amp;amp;lt;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.
Background Differentiation between Type 1 and Type 2 diabetes in adults is dif®cult at diagnosis.... more Background Differentiation between Type 1 and Type 2 diabetes in adults is dif®cult 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 classi®ed 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 classi®ed as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classi®ed. Results Among patients not classi®ed as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassi®ed 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 classi®ed 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 classi®ed 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 signi®cant 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 classi®cation is dif®cult 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.
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