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Diabet. Med. 28, 1045-1052 (2011) Abstract Aims In a cohort of men and women with Type 1 diabetes, prospectively followed for > 20 years, vibrotactile sense in fingers was investigated and related to neurophysiological tests, glycaemic level and clinical score. Methods Out of 58 patients, diagnosed at the age of 15-25 years and recruited 1984-1985, 32 patients (13 women, median age 52 years, range 44-75 years; 19 men, median age 52 years, range 39-69 years; median duration 33.5 years, range 21-52 years) accepted follow-up in 2006. Vibration thresholds were measured in finger pulps of index and little fingers bilaterally at seven frequencies and related to results of touch (monofilaments), tactile discrimination (two-point discrimination test), electrophysiology (median nerve function), glycaemic level (HbA1c levels since 1984-1985) and a clinical score. Results Vibrotactile sense was reduced in finger pulps, mainly in men, compared with an age- and gender-matched healthy control group with normal HbA1c. Vibration thresholds were increased, particularly at 250 and 500 Hz, in both index and little finger pulps. Touch and tactile discrimination correlated with vibration thresholds, but not with each other or with electrophysiology. HbA1c levels (at follow-up or mean values from five follow-ups since recruitment) did not correlate with any nerve function variables. Clinical scores correlated with vibrotactile sense, particularly at higher frequencies (> 125 Hz), but not with total Z-scores of electrophysiology. Duration of disease did not correlate with any variables. Conclusions Examination of vibration thresholds in index and little finger pulps may be valuable to detect neuropathy, where thresholds correlate with symptoms and tests. [ABSTRACT FROM AUTHOR]

Aim: To compare effects of early insulin vs. glibenclamide treatment on beta-cell function, metabolic control and quality of life (QL) in recently diagnosed patients with type 2 diabetes. Methods: Forty-nine patients with type 2 diabetes diagnosed 0–2 years before inclusion were randomized to two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide at six diabetic clinics in Sweden. C-peptide–glucagon tests were performed yearly after 3 days of withdrawal of treatment. Results: Thirty-four patients completed 4 years of study. Daily dose of insulin was increased from 20.4 ± 1.8 U at year 1 to 26.1 ± 2.9 U at year 4 (p = 0.005). Glibenclamide dosage increased from 2.7 ± 0.4 mg at year 1 to 4.5 ± 0.8 mg at year 4 (p = 0.02). Weight increased more in insulin than in glibenclamide treated (+4.4 ± 0.8 vs. +0.3 ± 1.0 kg, p < 0.005). Following short-term withdrawal of treatment, the C-peptide responses to glucagon were significantly higher in the insulin vs. glibenclamide group at years 1 (p < 0.01) and 2 (p < 0.02). HbA1c improved identical during the first year but thereafter deteriorated in the glibenclamide group (p < 0.005 for difference at year 4). Ratios of proinsulin to insulin were higher during treatment in glibenclamide- vs. insulin-treated patients after year 2. QL after 4 years as measured by the MOS 36-item Short-Form Health Survey (SF-36) form was not significantly altered. Conclusions: In a 4-year perspective, beta-cell function deteriorated in both groups. However, deterioration occurred faster in the glibenclamide group, indicating that alleviating demands on secretion by insulin treatment is beneficial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances. Methods Thirty-one patients with diabetes mellitus who complained of gastrointestinal symptoms were asked to complete a questionnaire about their symptoms. They were further investigated with oesophageal manometry and gastric emptying scintigraphy. Results Fifty-eight per cent of the patients had abnormal oesophageal function, and 68% had delayed gastric emptying. Abdominal fullness was the only symptom that related to any dysfunction, and it was associated with delayed gastric emptying ( P = 0.02). We did not find any relationship in motility or dysmotility between the oesophagus and the stomach. Conclusion Oesophageal dysmotility, as well as gastroparesis, are common in patients with diabetes who have gastrointestinal symptoms. It is important to investigate these patients further, to be able to reach an accurate diagnosis and instigate appropriate treatment. Our findings indicate that the oesophagus and the stomach function as separate organs and that pathology in one does not necessarily mean pathology in the other. [ABSTRACT FROM AUTHOR]

Aims The aim was to determine the course of islet cell antibodies [glutamate decarboxylase (GADA), tyrosine phosphatase-like islet antigen 2 (IA-2A) and islet cell (ICA)] after the diagnosis of the diabetic patient. Methods The Diabetes Incidence Study in Sweden (DISS) attempted to prospectively enrol all newly diagnosed diabetic patients aged 15–34 years during 1992 and 1993. C-peptide and autoantibody levels were determined from venous blood samples at diagnosis and again at yearly intervals for 6 years. Results After the first year, the odds of remaining GADA positive decreased by 9% per year [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.85–0.96] while the mean GADA index remained unchanged (  = 0.8, P = 0.37). There was no change in the percentage of subjects testing IA-2A positive after the first year (  = 0.1, P = 0.75). However, the mean index decreased 0.04 per year (95% CI: 0.03–0.05)—a 7.9% decline (95% CI: 5.4–10.4%). The odds of a subject testing positive for ICA decreased by 24% per year (OR = 0.76, 95% CI = 0.70–0.82). The mean ICA levels decreased 0.75 per year (95% CI: 0.66–0.84)—a 16.4% decline (95% CI: 14.1–18.6%). The rate of change in titres for all three autoantibodies was independent of gender, human leucocyte antigen genotype and C-peptide status. Conclusions GADA levels remained high while ICA levels declined. In contrast to a previous study, we found that the proportion of IA-2A subjects remaining positive did not decrease after the first year, while the average index decreased slightly. [ABSTRACT FROM AUTHOR]

Objective. To evaluate if exercise-induced ST-segment depression without typical angina pectoris is related to increases in sympatho-adrenal activity or β-adrenoceptor sensitivity. Patients. Thirteen patients (four men) aged 35–62 years with ST-segment depression during exercise but atypical symptoms and normal myocardial scintigraphy, and 13 matched controls. Design and interventions. Patients and controls were compared regarding responses with: (i) exercise testing without treatment, (ii) exercise testing following β-adrenoceptor blockade by propranolol (0.15 mg kg−1 i.v.), (iii) incremental adrenaline infusions (0.1, 0.2, 0.4 and 0.8 nmol kg−1 min−1) and (iv) adrenaline infusions during α-adrenoceptor blockade by phentolamine (0.5 mg min−1). Main outcome measures. ST-segment depression and tissue Doppler parameters reflecting contractility. Results. Exercise lowered the ST-segment by 2.44 mm without and 0.87 mm with β-adrenoceptor blockade ( P < 0.001 for difference) amongst patients, but not amongst controls. Maximal heart rate was slightly higher amongst patients ( P < 0.05), despite similar loads and plasma catecholamine responses to exercise in the two groups; this difference disappeared after β-adrenoceptor blockade with propranolol. ST-segment depression during adrenaline infusion was greater in patients compared with controls ( P < 0.01) despite similar increases in heart rate. α-Blockade enhanced the ST-segment depression ( P < 0.001) and heart rate ( P < 0.001) responses to adrenaline infusion more markedly amongst patients. Tissue Doppler imaging showed similar contractility and diastolic relaxation responses of patients and controls to adrenaline, but early diastolic movements did not increase amongst patients after phentolamine ( P < 0.01). Conclusions. Exercise-induced ST-segment depression in patients with a low likelihood of ischaemic heart disease is related to increased β-adrenergic sensitivity regarding chronotropic and electrophysiological, but not inotropic responses. [ABSTRACT FROM AUTHOR]

Aims: To examine the relationship between parasympathetic neuropathy, hyperinsulinaemia, glycaemic control (HbA1c), and future diabetic complications. Methods We assessed parasympathetic nerve function [expiration/inspiration (E/I) ratio], glomerular filtration rate (GFR), glycaemic control (HbA1c), fasting plasma (f-p-) C-peptide in 82 Type 2 diabetic patients (age 61 ± 1 years) 5 and 12-15 years after diagnosis. Diabetic retinopathy was assessed 15 years after diagnosis. Results High HbA1C values in the first study were associated with retinopathy (with 8.6 ± 2.0 vs. without retinopathy 6.2 ± 1.9%; P < 0.0001) and disturbed parasympathetic nerve function (low E/I ratio; rs = -0.41; P = 0.0061) in the second study, as well as with deteriorations in GFR between the first and second study (rs = 0.62; P < 0.0001). Patients with parasympathetic neuropathy in the first study had significantly higher f-p-C-peptide concentrations than those without 3 years (1.20 ± 0.43 vs. 0.86 ± 0.40 nmol/l; P = 0.00 15) and S years (1.20 ± 0.44 vs. 0.82 ± 0.33 nmol/l; P < 0.0001), but not 15 years after diagnosis. Conclusion High HbA1C values 5 years after diagnosis of Type 2 diabetes were associated with retinopathy, disturbed parasympathetic nerve function, and deterioration in GFR 7-10 years later. Parasympathetic neuropathy 5 years after diagnosis was associated with high C-peptide concentrations. Parasympathetic nerve function has to be considered when Β-cell function is evaluated. Hyperglycaemia is an important factor for the development of complications in Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Christensson AG, Grubb AO, Nilsson J-Å, Norrgren K, Sterner G, Sundkvist G (Malmö University Hospital, Malmö; and Lund University Hospital, Lund, Sweden). Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy.J Intern Med2004;256:510–518.To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age.Forty-one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and51Cr-EDTA clearance (reference method). Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created byz-scores for51Cr-EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular filtration rate (GFR) (51Cr-EDTA clearance) were 60 and 80 mL min−1 1.73 m−2, respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age-adjusted values (z-scores).Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus51Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when using age-adjusted values, the correlation for cystatin C and creatinine, respectively, versus51Cr-EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min−1 1.73 m−2 orz-scores<−1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min−1 1.73 m−2 orz-score−0.84 SD), serum cystatin C is significantly more useful.Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy. [ABSTRACT FROM AUTHOR]

AIMS: Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients. METHODS: Autonomic nerve function was assessed by heart-rate responses to deep breathing (E/I ratio) and tilting (acceleration and brake indices) and by the postural blood pressure reaction in 58 patients, 43 of whom were reassessed after 14 years. Nephropathy was evaluated by the degree of albuminuria (albuminuria > 20 micro g/min or > 0.03 g/24 h) and glomerular filtration rate ((51)Cr-EDTA plasma clearance). The acceleration index had deteriorated after 7 years (P = 0.0155), whereas the E/I ratio (P = 0.0070) and the diastolic postural blood pressure reaction (P = 0.0054) had deteriorated 14 years after the baseline examination (age-corrected values). All those with albuminuria at the third examination showed signs of autonomic neuropathy at baseline (10 of 10) compared with only nine of 22 without (P = 0.0016). Multiple regression analysis showed that the association between autonomic dysfunction and future albuminuria was due to the E/I ratio. In addition, individuals with an abnormal postural diastolic blood pressure fall (n = 7) at baseline showed a greater fall in glomerular filtration rate more than others 7-14 years later [29 (16.5) ml/min/1.72 m(2) vs. 11 (9) ml/min/1.72 m(2); P = 0.0074]. CONCLUSION: Autonomic nerve function had deteriorated after 14 years. Autonomic neuropathy and abnormal postural diastolic blood pressure falls at baseline were associated with future renal complications. Copyright 2004 Diabetes UK [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Schölin A, Björklund L, Borg H, Arnqvist H, Björk E, Blohmé G, Bolinder J, Eriksson JW, Gudbjörnsdottir S, Nyström L, Östman J, Karlsson AF, Sundkvist G (Uppsala University Hospital, Uppsala; Malmö University Hospital, Malmö; Linköping University Hospital, Linköping; South Stockholm General Hospital, Stockholm; Huddinge University Hospital, Huddinge; Umeå University Hospital, Umeå; Sahlgrenska University Hospital, Gothenburg; Umeå University, Umeå, Sweden). Islet antibodies and remaining β-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden. J Intern Med 2004; 255: 384–391. To 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. Population-based cohort study. Nationwide from all Departments of Medicine and Endocrinology in Sweden. A total of 312 young (15–34 years old) adults diagnosed with diabetes during 1987–88. Plasma 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. Amongst 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. Sixteen 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Aims To clarify if cardiovascular autonomic neuropathy is associated with carotid artery atherosclerotic plaques in Type 2 diabetic patients. Methods Cardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients 5–6 years after diagnosis of diabetes. Results Cardiovascular autonomic neuropathy [abnormal age corrected expiration/inspiration (E/I) ratio or acceleration index (AI)] was found in 13/61 (21%) patients. Patients with cardiovascular autonomic neuropathy showed increased degree of stenosis in the common carotid artery (24.6 ± 13.2% vs. 14.7 ± 9.2%; P = 0.014) and a tendency towards a higher plaque score (4.0 ± 1.7 vs. 3.2 ± 1.6; P = 0.064). Controlled for age, AI correlated inversely with degree of stenosis (r = -0.39; P = 0.005), plaque score (r = -0.39; P = 0.005), and mean (r = -0.33; P = 0.018) and maximum (r = -0.39; P = 0.004) intima-media thickness in the common carotid artery. In contrast, E/I ratio correlated only slightly with mean intima-media thickness in the common carotid artery (r = -0.28; P = 0.049). Conclusions Cardiovascular autonomic neuropathy was associated with carotid atherosclerosis in Type 2 diabetic patients. Abnormal E/I ratios reflect efferent structural damage to parasympathetic nerves whereas abnormal AI reflects afferent autonomic dysfunction possibly due to impaired baroreceptor sensitivity secondary to carotid atherosclerosis. Diabet. Med. 20, 495–499 (2003). [ABSTRACT FROM AUTHOR]

Reports that female gender increases the stifness of elastic but not of muscular arteries in type 1 diabetes patients. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on clinical physiology and functional imaging.

The aim of this study was to quantify the reflex sympathetic vasoconstriction in skin at different depths. Twenty healthy subjects were studied. Finger skin blood flow was measured using laser Doppler perfusion imaging (LDPI) and laser Doppler perfusion monitoring (LDPM). In LDPM, a probe with fibres separated 0·25 mm (deep) and 0·14 mm (superficial) from the illuminating fibre was used. Local heating (40°C) was achieved with a Peltier element, and reflex vasoconstriction induced by immersion of the contra-lateral hand and forearm for 3 min in water at 15°C. The change in skin blood flow was measured and a vasoconstriction index (VAC: cooling/before cooling) calculated. VAC indices of LDPI, LDPM-0·25 and LDPM-0·14 were 0·60, 0·59 and 0·60, respectively. The two components of the LDPM perfusion value, blood cell velocity and concentration, were studied separately. Their contributions in LDPM-0·25 were roughly the same, whereas the velocity component dominated in LDPM-0·14, although their relative responses in the two channels were similar. We conclude that sympathetic skin vasoconstriction does not significantly differ in two compartments, as probed with fibres separated by 0·25 and 0·14 mm. Blood cell velocity is influenced in a proportional way, as is concentration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstracts Aims Sorbitol and myo-inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. Methods After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas–liquid chromatography/mass spectrometry. Results Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) μV and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6) μV; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo-inositol levels correlated, however, positively with cluster density (rs = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) μV; P = 0.0246) and myelinated nerve fibre density (MNFD; 4076 (1091) vs. 5219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. Conclusions Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo-inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density). [ABSTRACT FROM AUTHOR]

The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase-like protein IA2 antibodies (IA2-ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type I diabetes. The aim of this study was to compare the frequency of ICA and GADA and/or IA2-ab not only at, but also after the diagnosis of diabetes. ICA, GADA and IA2-ab were therefore assessed at and up to 11 y after the diagnosis of diabetes in 86 children (1-15-y-old). At diagnosis, ICA were found in 74 (86%) and GADA and/or IA2-ab in 79 (92%) of the diabetic children. Hence, there was no major difference in frequency between ICA and GADA and/or IA2-ab at diagnosis of diabetes. At follow-up, however, ICA were less frequent than GADA and/or IA2-ab; 1-3 y after diagnosis ICA were found in 12 (44%) and GADA and/or IA2-ab in 24 (89%) of 27 children (p=0.001); 4-6 y after diagnosis ICA were found in 7 (24%) and GADA and/or IA2-ab in 27 (93%) of 29 children (p < 0.0001); 7-11 y after diagnosis ICA were found in 4 (13%) and GADA and/or IA2-ab in 21 (70%) of 30 children (p < 0.0001). We conclude that the frequency of ICA does not always correspond to that of GADA and/or IA2-ab. Many years after diagnosis of diabetes, measurements of GADA and IA2-ab, but not ICA, detect autoimmunity in high frequency. [ABSTRACT FROM AUTHOR]

SummaryAims The increase in risk for cardiovascular complications in diabetic women is even greater than that in diabetic men. We found arterial stiffness to be increased in women, but not in men, with Type 1 diabetes mellitus (DM). The aims of the present study were to evaluate whether the changes in arterial distensibility are influenced by diabetes duration and to evaluate any association between autonomic neuropathy and decreased arterial distensibility. Methods Stiffness of the abdominal aorta was measured noninvasively using echo-tracking sonography and parasympathetic function by heart rate variation during deep breathing (E/I ratio) in 40 women (mean age 33 years, range 20–61) and 38 men (mean age 36 years, range 22–56) with Type 1 DM. Results There was a significant correlation between aortic stiffness and duration of diabetes in women (r = 0.41, P = 0.008), but not in men (r = 0.15, P = 0.35). There was also a significant correlation between aortic stiffness and the E/I ratio in women (r = – 0.49, P = 0.002), but not in men (r = – 0.14, P = 0.41). When adjusted for diabetes duration, the significant association between the E/I ratio and aortic stiffness remained in diabetic women (r = – 0.44, P = 0.008) and was stronger than the association between diabetes duration and aortic stiffness. There were no significant correlations between aortic stiffness and triglycerides or total cholesterol, respectively. Conclusions Increased aortic wall stiffness found in women with Type 1 DM is related to diabetes duration. Further, in women with Type 1 DM there is a correlation between increased aortic stiffness and parasympathetic dysfunction. This may be of importance for the increased susceptibility to cardiovascular complications in diabetic women. Diabet. Med. 16, 291–297 (1999). [ABSTRACT FROM AUTHOR]

Aims To clarify whether parasympathetic neuropathy in Type 2 diabetic patients is associated with features of the insulin resistance syndrome. Methods Blood pressures, glycaemic control (HbA1c), plasma lipids, residual β-cell function (fasting plasma C-peptide), autonomic nerve function, urinary albumin excretion and glomerular filtration rate (Cr-EDTA clearance) were evaluated in 82 Type 2 diabetic patients (age 61 ± 1 years) 5 years after diagnosis of diabetes. Results Parasympathetic neuropathy (an abnormal age corrected E/I ratio) was found in 24/82 (29%) patients. After adjustment for body mass index (BMI), patients with parasympathetic neuropathy had elevated fasting plasma C-peptide (P < 0.001) and triglyceride (Tg) (P < 0.05) levels compared with patients without parasympathetic neuropathy. In addition, the age corrected E/I ratio correlated inversely with Tg (r = –0.31; P < 0.01) and fasting plasma C-peptide (r = – 0.32; P < 0.01) in the Type 2 diabetic patients. Conclusion Autonomic neuropathy 5 years after diagnosis of Type 2 diabetes is associated with an unfavourable metabolic risk profile. Diabet. Med. 16, 49–54 (1999). [ABSTRACT FROM AUTHOR]

Objectives: To examine the relationship between previous glycaemic exposure and prevalence of retinopathy 8 years after diagnosis of diabetes in 58 islet cell antibodies (ICA)-negative noninsulin-dependent diabetes mellitus (NIDDM) patients and in a group of 14 ICA-positive 'NIDDM' and insulin-dependent diabetes mellitus (IDDM) patients.Design and Methods: The Wisconsin retinopathy scale was used to assess the retinopathy which was graded into mild, moderate and severe nonproliferative diabetic retinopathy (NPDR), or proliferative retinopathy (PDR). The frequency and severity of retinopathy was related to HbA1c levels at diagnosis, and 3 and 5 years later.Results: Thirty of the 58 ICA-negative NIDDM patients (52%) but only 2 of the 14 ICA-positive 'NIDDM' or IDDM patients (14%) had mild-moderate-severe NPDR 8 years after diagnosis (P = 0.02). None had PDR. Retinopathy 8 years after diagnosis in NIDDM (= 58 ICA-negative patients) was correlated with the degree of glycaemic control (HbA1c levels) at 3 and 5 years after diagnosis, but not to HbA1c levels at diagnosis. The relative risk for a higher average HbA1c (per percentage) at 3 and 5 years was 1.56 for any retinopathy vs. no retinopathy (95% confidence interval 1.1-2.2; P = 0.01) and 1.68 for moderate to severe NPDR in comparison with no DR and mild NPDR (95% confidence interval 1.0-2.8; P = 0.04).Conclusions: Retinopathy after 8 years of diabetes in NIDDM patients was associated with impaired glycaemic control during previous years but not with glycaemic control at baseline. Good glycaemic control may prevent retinopathy in patients with NIDDM. [ABSTRACT FROM AUTHOR]

Objective: Sural nerve pathology in peripheral neuropathy shows correlation with clinical findings and neurophysiological tests. The aim was to investigate progression of nerve dysfunction over time in relation to a baseline nerve biopsy., Methods: Baseline myelinated nerve fiber density (MNFD) was assessed in sural nerve biopsies from 10 men with type 2 diabetes, 10 with impaired and 10 with normal glucose tolerance. Nerve conduction and quantitative perception thresholds were estimated at baseline and follow-up (7-10 years later)., Results: Subjects with low MNFD (< or = 4700 fibers/mm(2)) showed decline of peroneal amplitude (P < 0.02) and conduction velocity (P < 0.04), as well as median nerve sensory amplitude (P < 0.05) and motor conduction velocity (P < 0.04) from baseline to follow-up. In linear regression analyses, diabetes influenced decline of nerve conduction. MNFD correlated negatively with body mass index (r = -0.469; P < 0.02)., Conclusion: Low MNFD may predict progression of neurophysiological dysfunction and links obesity to myelinated nerve fiber loss.

Objectives: To detect post-operative sequelae of sural nerve biopsy., Materials and Methods: A questionnaire mailed to type 1 diabetic patients (n = 24; male/female 23/1; reply n = 23) 2 years after biopsy., Results: Type 1 diabetic patients (age 56 [11]; median [interquartile range]) had a long duration of diabetes (DM; 20 [19] years) and all had neuropathy. Three out of 24 patients developed infection (two superficial and one deep) and one had a post-operative bleeding. Less frequent pain among the patients were reported from one centre. About one-third or more of the patients still complained of pain, mostly mild, in the biopsy area and paraesthesia in the foot 2 years after surgery. More than two-thirds of the patients were reluctant for further biopsy; a crucial information in drug trial planning., Conclusions: Sequelae of a sural nerve biopsy occur in type 1 DM. The risk for wound infections should be considered.

Background: The role of non-specific inflammation in beta-cell loss in type 1 diabetes is unclear. In the present study, inflammatory markers were determined in patients with newly diagnosed disease and related to beta-cell function, glycemic control and autoimmunity., Methods: Ninety-seven adult patients with type 1 diabetes mellitus (80% islet antibody positives, ab(+)) were examined at diagnosis and 3, 6, 9 and 12 months after the start of insulin treatment. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, islet autoantibodies, insulin requirement and HbA(1c) were assessed., Results: The concentrations of CRP were high-normal at diagnosis and did not change during the study period. A positive correlation between CRP at diagnosis and BMI was observed in ab(+) as well as in ab(-) cases. Detectable concentrations of IL-6 were found in 32% (157/485) of the samples and did not change during the study. Ab(-) patients had higher values of CRP at diagnosis and throughout the study compared to the ab(+). Among the ab(+) patients, CRP concentrations during the study were positively correlated to C-peptide at 12 months and an increase in HbA(1c) levels between 6 and 12 months. No associations between the presence or levels of islet autoantibodies and CRP were noted., Conclusions: In type 1 diabetes, the islet destructive process and the development of beta-cell remission are not associated with changes in CRP or IL-6. Instead, elevated CRP concentrations are prevalent and seem to reflect insulin resistance, as positive associations to BMI, C-peptide and deterioration of glycemic control were observed., (Copyright 2003 John Wiley & Sons, Ltd.)

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., (Copyright 2000 John Wiley & Sons, Ltd.)