| 1. |
- Törn, Carina, et al.
(författare)
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Combinations of beta cell specific autoantibodies at diagnosis of diabetes in young adults reflects different courses of beta cell damage
- 2001
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Ingår i: Autoimmunity. - 0891-6934. ; 33:2, s. 115-120
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Tidskriftsartikel (refereegranskat)abstract
- 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 (1A-2A) were followed prospectively thr 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).
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| 5. |
- Östman, Jan, et al.
(författare)
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Ketoacidosis in young adults is not related to the islet antibodies at the diagnosis of Type 1 diabetes mellitus - A nationwide study
- 2000
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 17, s. 269-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To test the hypothesis that there is lower prevalence of islet antibodies in subjects with newly diagnosed Type 1 diabetes mellitus in young adulthood than in children is associated with less severe diabetes at time of diagnosis. Methods: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of 15-34-year-old newly diagnosed diabetic subjects. During 1992-1993, all diabetic subjects (excluding secondary and gestational diabetes) were reported on standardized forms, with information about clinical characteristics at diagnosis. The study examined islet cell antibodies (ICA) by indirect immunofluorescence, and autoantibodies to glutamic acid decarboxylase (GADA), tyrosine phosphatase- like antigen (IA-2A) and insulin (IAA) as well as C-peptide by radioimmunoassay. Results: Blood samples were available from 78 patients with diabetic ketoacidosis (DKA) and 517 non-acidotic patients. The prevalence of ICA (63% vs. 57%), GADA (63% vs. 66%), IA-2A (35% vs. 44%) and IAA (20% vs. 15%) were very similar in patients with or without DKA. The median levels of the four autoantibodies did not differ between the two groups. High blood glucose (P < 0.001) and low C-peptide levels (P < 0.001) were the only parameters found to be related to DKA. Conclusions: The similarities in findings of newly diagnosed diabetic patients with or without DKA regarding ICA, GADA, IA-2A and IAA suggest that there is no relationship between the expression of antigenicity and the severity of β-cell dysfunction. The lower prevalence of the four autoantibodies in 15-34-year-old diabetic subjects compared with previous findings in children is not explained by misclassification of diabetes type.
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| 6. |
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| 7. |
- Hagstrom-Toft, E, et al.
(författare)
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Marked heterogeneity of human skeletal muscle lipolysis at rest
- 2002
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3376-3383
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Tidskriftsartikel (refereegranskat)abstract
- In this study, variations in lipolysis among different muscle groups were examined by measuring local net glycerol release in vivo in healthy, normal-weight subjects (n = 11) during rested, postabsorptive conditions. Microdialysis of the gastrocnemius, deltoid, and vastus lateralis muscle regions revealed that extracellular glycerol concentrations of these three muscle regions were 84.7 ± 6.7, 59.7 + 7.3, and 56.4 ± 7.5 μmol/l, respectively, and the arterial plasma glycerol concentration was 44.8 ± 2.3 μmol/l (P = 0.0003–0.006, gastrocnemius vs. others). Local tissue blood flow, as measured by Xe clearance, did not differ among the regions. Net glycerol release was significantly higher in gastrocnemius muscle than in the two other regions. There were no regional differences in glycerol uptake when studied during glycerol infusion. Gastrocnemius muscle showed a dominance of type 1 fibers (70%), whereas the vastus lateralis muscle had equal distribution of fiber types (P = 0.02). No differences in intramuscular triaclyceride content, perimuscular fat, or the adipocyte-specific protein perilipin were observed among the muscle regions. Triglyceride turnover in the gastrocnemius muscle was 3.3 + 1.4% over 24 h, which is about 10 times more rapid than the turnover rate in subcutaneous adipose tissue (P < 0.01). Thus there were marked differences in lipolytic activity among skeletal muscle groups at rest, possibly reflecting variations in fiber type.
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| 8. |
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| 9. |
- Littorin, Bengt, et al.
(författare)
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Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS)
- 2003
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 254:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Pundziute-Lycka, A, et al.
(författare)
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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 to 1998
- 2002
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 45:6, s. 783-791
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 11. |
- Pundziute-Lyckå, A, et al.
(författare)
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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.
- 2002
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 45:6, s. 783-91
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
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| 13. |
- Schölin, Anna, et al.
(författare)
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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
- 2004
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:3, s. 384-391
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- ObjectivesTo establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later.DesignPopulation-based cohort study.SettingNationwide from all Departments of Medicine and Endocrinology in Sweden.SubjectsA total of 312 young (15–34 years old) adults diagnosed with diabetes during 1987–88.Main outcome measurePlasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-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.ResultsAmongst 269 islet antibody positives (ab+) at diagnosis, preserved β-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 β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up.ConclusionsSixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.
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| 14. |
- Schölin, Anna, et al.
(författare)
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Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes
- 2004
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 21:5, s. 447-455
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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 HbA1c and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose ≤ 0.3 U/kg/24 h and HbA1c within the normal range, was analysed in relation to characteristics at diagnosis.Results Remissions were seen in 43% of the patients with a median duration of 8 months (range 1–73). Sixteen per cent had a remission with a duration > 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/m2) 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.
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| 19. |
- Bolinder, J, et al.
(författare)
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Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects
- 2000
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 49:5, s. 797-802
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle and adipose tissue lipolysis rates were quantitatively compared in 12 healthy nonobese and 14 insulin-resistant obese subjects for 3.5 h after an oral glucose load using microdialysis measurements of interstitial glycerol concentrations and determinations of local blood flow with 133Xe clearance in the gastrocnemius muscle and in abdominal subcutaneous adipose tissue. Together with measurements of arterialized venous plasma glycerol, the absolute rates of glycerol mobilization were estimated. In the basal state, skeletal muscle and adipose tissue glycerol levels were 50% higher (P < 0.05-0.01) and adipose tissue blood flow (ATBF) and muscle blood flow (MBF) rates were 30-40% lower (P < 0.02-0.05) in obese versus nonobese subjects. After glucose ingestion, adipose tissue glycerol levels were rapidly and transiently reduced, whereas in muscle, a progressive and less pronounced fall in glycerol levels was evident. MBF remained unchanged in both study groups, whereas ATBF increased more markedly (P < 0.01) in the nonobese versus obese subjects after the oral glucose load. The fasting rates of glycerol release per unit of tissue weight from skeletal muscle were between 20 and 25% of that from adipose tissue in both groups. After glucose ingestion, the rates of glycerol release from skeletal muscle and from adipose tissue were almost identical in nonobese and obese subjects. However, the kinetic patterns differed markedly between tissues; in adipose tissue, the rate of glycerol mobilization was suppressed by 25-30% (P < 0.05) after glucose ingestion, whereas no significant reduction was registered in skeletal muscle. We conclude that significant amounts of glycerol are released from skeletal muscle, which suggests that muscle lipolysis provides an important endogenous energy source in humans. In response to glucose ingestion, the regulation of skeletal muscle glycerol release differs from that in adipose tissue; although the rate of glycerol release from adipose tissue is clearly suppressed, the rate of glycerol mobilization from skeletal muscle remains unaltered. In quantitative terms, the rate of glycerol release per unit of tissue weight in adipose tissue and in skeletal muscle is similar in nonobese and obese subjects in both the postabsorptive state and after glucose ingestion.
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| 20. |
- Borg, A., et al.
(författare)
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Simultaneous velocity and concentration measurements in the near field of a turbulent low-pressure jet by digital particle image velocimetry-planar laser-induced fluorescence
- 2001
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Ingår i: Experiments in Fluids. - : Springer Science and Business Media LLC. - 0723-4864 .- 1432-1114. ; 31:2, s. 140-152
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Tidskriftsartikel (refereegranskat)abstract
- The main purpose of this work is to develop a method for simultaneous measurement of velocity and passive scalar concentration by means of digital particle image velocimetry and planar laser-induced fluorescence. Details of the implementation of the method are given, and the technique is applied to measurements of concentration and velocity in the centre-plane of a liquid jet with a Reynolds number of 6,000. The measurements are compared with large eddy simulations. Mean velocities and concentrations, fluctuating velocities and concentrations, and correlation between fluctuating velocities and concentrations. are analysed for the first six diameters downstream of the jet exit. The general agreement between measured and simulated results was found to be good, in particular for mean quantities. Mean profiles are also found to be in good agreement with other experimental work on jets reported in the literature. The whole-plane measurement method was found to be very useful for detailed comparisons of turbulent statistics with simulated data. The inadequacy of models for turbulent mass transport based on the standard gradient diffusion concept is demonstrated through the experimental data.
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| 21. |
- Borg, Henrik, et al.
(författare)
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Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS)
- 2003
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 46:2, s. 173-181
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis. We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. Methods. During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. Results. In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. Conclusion/interpretation. Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.
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| 24. |
- Hagstrom-Toft, E, et al.
(författare)
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Evidence for a major role of skeletal muscle lipolysis in the regulation of lipid oxidation during caloric restriction in vivo
- 2001
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 50:7, s. 1604-1611
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Tidskriftsartikel (refereegranskat)abstract
- A lipolytic process in skeletal muscle has recently been demonstrated. However, the physiological importance of this process is unknown. We investigated the role of skeletal muscle lipolysis for lipid utilization during caloric restriction in eight obese women before and after 11 days of very low–calorie diet (VLCD) (2.2 MJ per day). Subjects were studied with indirect calorimetry and microdialysis of skeletal muscle and adipose tissue in order to analyze substrate utilization and glycerol (lipolysis index) in connection with a two-step euglycemic-hyperinsulinemic (12 and 80 mU/m2 · min) clamp. Local blood flow rates in the two tissues were determined with 133Xe-clearance. Circulating free fatty acids and glycerol decreased to a similar extent during insulin infusion before and during VLCD, and there was a less marked insulin-induced reduction in lipid oxidation during VLCD. Adipose tissue glycerol release was hampered by insulin infusion to the same extent (∼40%) before and during VLCD. Skeletal muscle glycerol release was not influenced by insulin before VLCD. However, during VLCD insulin caused a marked (fivefold) (P < 0.01) increase in skeletal muscle glycerol release. The effect was accompanied by a fourfold stimulation of skeletal muscle blood flow (P < 0.01). We propose that, during short-term caloric restriction, the reduced ability of insulin to inhibit lipids, despite a preserved antilipolytic effect of the hormone in adipose tissue, is caused by an augmented mobilization of fat from skeletal muscle, and that a physiological role of muscle lipolysis provides a local source of fatty acids.
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| 26. |
- Moberg, E, et al.
(författare)
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No apparent suppression by insulin of in vivo skeletal muscle lipolysis in nonobese women
- 2002
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Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 283:2, s. E295-E301
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the antilipolytic effect of insulin in skeletal muscle and adipose tissue in vivo, the rates of glycerol release from the two tissues were compared in 10 nonobese women during a two-step euglycemic hyperinsulinemic clamp. Tissue interstitial glycerol levels were determined by microdialysis, and tissue blood flow was assessed with the 133Xe clearance technique. Absolute rates of glycerol release were estimated according to Fick's principle. In both adipose tissue and muscle, glycerol levels decreased significantly already during the low insulin infusion rate. The fractional release of glycerol (difference between interstitial glycerol and arterialized venous plasma glycerol) was reduced by more than one-half in adipose tissue ( P < 0.0001) in response to insulin, whereas it remained unaltered in skeletal muscle. Muscle blood flow rates increased by 60% ( P < 0.02) during insulin infusion; in adipose tissue, blood flow rates did not change significantly in response to insulin. The basal rate of glycerol release from skeletal muscle amounted to ∼15% of that from adipose tissue. After insulin infusion, the rate of adipose tissue glycerol release was markedly suppressed, whereas in skeletal muscle the rate of glycerol mobilization did not change significantly in response to insulin. It is concluded that insulin does not inhibit the rate of lipolysis in skeletal muscle of nonobese women.
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| 30. |
- Sjöberg, S, et al.
(författare)
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Residual insulin secretion is not coupled to a maintained glucagon response to hypoglycaemia in long-term type 1 diabetes.
- 2002
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 252:4, s. 342-351
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the influence of residual beta-cell function on glucagon secretion and glucose counter-regulation following hypoglycaemia in type 1 diabetes. DESIGN AND SUBJECTS: The hormonal counter-regulatory responses to standardized insulin-induced hypoglycaemia were investigated, 18 patients with type 1 diabetes of long duration and 12 healthy subjects were investigated. Nine of the diabetic patients (diabetes duration 17 +/- 1 years) had residual insulin secretion, as reflected by persistent urinary C-peptide excretion. The other nine diabetic patients (diabetes duration 21 +/- 1 years) were C-peptide negative. RESULTS: Similar hypoglycaemic nadirs were found in all groups (2.1-2.3 mmol L-1), whereas the recovery of plasma glucose levels was delayed similarly in the diabetic groups. In the control subjects, plasma glucagon increased ( approximately 50%). No significant glucagon response was registered in either of the two diabetic groups. The maximum plasma adrenaline and pancreatic polypeptides (PP) responses to hypoglycaemia were comparable in the two diabetic patient groups; the peak values being lower (P < 0.05) than in the controls. Plasma noradrenaline, growth hormone and cortisol responses to hypoglycaemia were similar in all three groups. CONCLUSION: Residual beta-cell function in patients with long-term type 1 diabetes is not accompanied by preservation of the glucagon response to hypoglycaemia. As the two markers of autonomic function (adrenaline and PP) were similarly reduced in the two diabetic groups, the findings instead favour the concept that the defective glucagon secretory response to hypoglycaemia is because of autonomic nervous dysfunction.
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