Biomedical subjects

C D Agardh

Publications and source records attributed to C D Agardh.

At least 37 records · Page 2Linked to original sources

PubMed1998

Hypoglycaemia leads to an increased QT interval in normal men.

Hypoglycaemia is presumed to be the cause of death in about 3% of insulin-treated diabetic patients. Some of these patients suffer from hypoglycaemic brain damage, but the majority have no evident brain damage and are supposed to have died from other causes such as a cardiac arrhythmia. The putative mechanism is a hypoglycaemia-induced prolongation of the QT interval which increases the risk of malignant ventricular tachycardia. The aim of the present study was to examine the electrocardiogram during and after hypoglycaemia in healthy men. To that end, hypoglycaemia was induced by an intravenous infusion of insulin (2.5 mU kg-1 min-1) in 10 healthy men to reach a venous blood glucose level of 2.1 +/- 0.3 mmol l-1 for 65 +/- 9 min. Before hypoglycaemia, after 20 and 50 min of hypoglycaemia and 20 and 45 min after normalization of the blood glucose, the QT interval was measured by a ruler and corrected for the heart rate. Results are given as mean +/- SD and comparisons were made with an ANOVA, except for symptom scores and plasma adrenaline where non-parametric tests were used. When this indicated significance, further analysis was performed with a two-tailed t-test. During hypoglycaemia the corrected QT interval increased from 380 +/- 20 ms1/2 to 440 +/- 30 ms1/2 (P < 0.001), and the amplitude of the T wave decreased (P = 0.002). The serum potassium level decreased from 4.3 +/- 0.3 mmol l-1 to 3.5 +/- 0.2 mmol l-1 (P < 0.001) and the plasma adrenaline concentration increased from 0.20 +/- 0.04 nmol l-1 to 2.46 +/- 2.58 nmol l-1 (P < 0.01). The results of this study confirm that a prolongation of the QT interval occurs during hypoglycaemia, but the significance of this finding still has to be proven.

Adult↗

PubMed1998

The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not influenced by aminoguanidine treatment.

PURPOSE: To examine the levels of the free radical protecting enzyme glutathione and the endothelial/pericyte ratio in retinal capillaries in the Goto-Kakizaki (GK) Wistar rat, with and without aminoguanidine treatment. METHODS: Eight-month-old GK rats, with non-obese, spontaneous non-insulin-dependent diabetes mellitus (NIDDM), were examined after a six month period of aminoguanidine treatment. Glutathione levels were measured with high performance liquid chromatography and the endothelial/pericyte ratio was calculated in trypsin digested vessel preparations. RESULTS: The levels of glutathione in GK rat retina were significantly lower compared to controls (p = 0.0108). There was no difference in the endothelial/pericyte ratio compared to matched control rats (1.8 +/- 0.2 vs. 1.8 +/- 0.1, respectively). Aminoguanidine treatment did not influence either the degree of hyperglycemia, the levels of glutathione or the endothelial/pericyte ratio in GK or control rat retina. CONCLUSIONS: The results indicate that impaired glucose metabolism may influence one of the defense mechanisms for oxidative stress, but also suggest that decreased glutathione levels occur prior to morphological signs of pericyte loss and/or endothelial cell proliferation in this animal model of hereditary NIDDM.

Animals↗

PubMed1998

Long-term prognosis after healed amputation in patients with diabetes.

In this prospective study, mortality, rehabilitation, and new amputations on the same or on the contralateral leg were studied in 189 patients with diabetes who had achieved healing of an index amputation. Ninety-three patients had achieved healing after an index minor (below the ankle) and 96 after an index major (above the ankle) amputation, precipitated by a foot ulcer. The healing time was 29 weeks (range, 3-191 weeks) with a minor amputation and 8 weeks (range, 3-104 weeks) with a primary major amputation. The mortality 1, 3, and 5 years after the index amputation was 15%, 38%, and 68%, respectively, and was higher in patients who had achieved healing after major amputation than in patients achieving healing after minor amputation. The rate of new amputations after 1, 3, and 5 years of observation was 14%, 30%, and 49%, respectively. There was no difference among patients with an index minor and those with an index major amputation. The rate of new major amputations was 9%, 13%, and 23%, respectively, and was higher in patients with an index major amputation. Eighty-five percent of new amputations were precipitated by a foot ulcer. Patients living independently before the index amputation returned to living independently more often after a minor than a major amputation (93% versus 61%). One year after the index amputation, 70% of patients who had achieved healing after having a minor amputation and who could walk 1 km or more before amputation had regained this walking capacity, compared with 19% of patients having a major amputation. Seventy percent of patients with an index transtibial amputation who could walk before amputation were fitted with a prosthesis, and 52% were using it regularly. Patients with diabetes who had an index major amputation had a higher mortality, an equal rate of new amputation, and a lower rehabilitation potential than did patients who had an index minor amputation.

Adult↗

PubMed1997

Pre-eclampsia is a potent risk factor for deterioration of retinopathy during pregnancy in Type 1 diabetic patients.

The aim of the present study was to examine the influence of pregnancy on deterioration of retinopathy in patients with Type 1 diabetes mellitus. Sixty-five pregnant Type 1 diabetic women attending the University Hospital in Lund were studied retrospectively. The degree of retinopathy, and levels of HbA1c and blood pressure 12 months before, during, and 6 months after pregnancy were compared of those of 56 non-pregnant Type 1 diabetic women matched for age and duration of diabetes. For all patients, sight-threatening deterioration of retinopathy did not differ between the pregnancy group (9/65) and the control group (6/56). Over time, pregnant patients had lower HbA1c levels than controls (p < 0.001). Pregnant patients with sight-threatening deterioration of retinopathy had higher HbA1c levels than those without (p = 0.028 and the decrement in HbA1c between the 6-14th and the 20th week of gestation was more pronounced (p = 0.006). In those patients who developed pre-eclampsia during pregnancy, deterioration of retinopathy ocurred more frequently compared to those without pre-eclampsia (4/8 vs 5/65; p = 0.005). In conclusion, sight-threatening deterioration of retinopathy was not more common during pregnancy in IDDM patients than among age- and duration-matched control patients. In pregnant patients, deterioration of retinopathy was associated with the pregestational degree of metabolic control as well as with a rapidly improved glycaemic control acheived during pregnancy. Among those in whom deterioration occurred during pregnancy, pre-eclampsia was a potent risk factor.

Adult↗

PubMed1997

Burden of illness, metabolic control, and complications in relation to depressive symptoms in IDDM patients.

Relationships between demographic-, treatment-, and sickness-related factors, metabolic control (HbA1c), perceived burden of illness, and degree of depressive symptoms were examined in a group of 155 insulin-dependent diabetic patients, aged 35.3 +/- 8.9 years. The patients completed a questionnaire measuring depressive symptoms and three aspects of perceived burden of illness. No gender differences in HbA1c level or occurrence of late diabetic complications were found. Both men and women showed a modestly elevated degree of depression compared with norm groups. Self-reported burden of illness was strongly related to depression but was largely unrelated to objective disease-related measures. Level of depression was correlated neither with degree of metabolic control nor with the presence of such late diabetic complications as retinopathy and nephropathy. Some 44% of the variance in depression could be explained by worries about complications in those patients with the lowest HbA1c levels, by perceived restrictions in everyday life in patients with intermediate metabolic control, and by problems of glycaemic regulation in patients with poor metabolic control. Degree of depression was largely unrelated to disease severity, but was found to be related to the perceived daily burden of living with the disease, the specific worries and concerns associated with a depressed mood varying with degree of metabolic control.

Adult↗

PubMed1997

The association between retinopathy, nephropathy, cardiovascular disease and long-term metabolic control in type 1 diabetes mellitus: a 5 year follow-up study of 442 adult patients in routine care.

The aim of the present study was to examine mean HbA1c and blood pressure levels during a 5 year period in 442 type 1 adult diabetic patients in relation to the incidence and progression of retinopathy, nephropathy and to cardiovascular morbidity and mortality. The study showed, that in patients under routine care at a diabetic unit with four visits to the out-patient clinic per year, the intraindividual coefficient of variation for HbA1c values was 11 +/- 4% (mean +/- S.D.), and 7 +/- 3 and 8 +/- 2% for systolic and diastolic blood pressure, respectively. In 121 patients without retinopathy at entry, the 5 year incidence of any retinopathy was 47% (n = 57). Patients who developed retinopathy had higher mean HbA1c levels (P < 0.01), as well as mean systolic (P < 0.01) and diastolic (P < 0.05) blood pressure levels. In 123 patients with background retinopathy at entry, progression to severe retinopathy, i.e. clinically significant macular oedema, severe non-proliferative or proliferative retinopathy, occurred in 41% (n = 51). In those patients, the degree of metabolic control was worse (P < 0.001), the systolic (P < 0.05) and diastolic (P < 0.01) blood pressure levels were higher. The patients were stratified into four groups according to their urinary albumin concentration at entry: (1) normal albuminuria (< 12.5 mg/l), (2) borderline albuminuria (12.5-30 mg/l), (3) microalbuminuria (31-299 mg/l), i.c. incipient nephropathy and (4) clinical nephropathy (> or = 300 mg/l). An increase of urinary albumin concentration in patients who had normoalbuminuria or borderline albuminuria at entry was associated with mean HbA1c levels (r = 0.24, P < 0.01 and r = 0.27, P < 0.01, respectively). No such association was seen in patients with microalbuminuria or clinical nephropathy at entry. There was no association between the increase of urinary albumin level and mean systolic blood pressure levels in patients who had normoalbuminuria and microalbuminuria at entry. In contrast, there was an association between the increase of urinary albumin level in patients with borderline albuminuria (r = 0.36, P < 0.001), clinical nephropathy (r = 0.26, P < 0.05) and mean systolic blood pressure (P < 0.05). There was no association between the increase of urinary albumin levels and mean diastolic blood pressure in any of the albuminuria groups. As for the incidence of cardiovascular disease, renal insufficiency or death, the duration of diabetes (P < 0.01), urinary albumin concentration at entry (P < 0.001), mean systolic blood pressure (P < 0.05) and treatment with loop diuretics (P < 0.001) were but age, age at onset of diabetes, mean levels of HbA1c and diastolic blood pressure as well as treatment with beta- or Ca-blockers or ACE inhibitors were not related to these end-points. In conclusion, the present study showed that there was an association between the degree of metabolic control and both development and progression of retinopathy and progression of nephropathy of early stages in type 1 diabetic patients treated under routine conditions. Moreover, both the incidence and progression of retinopathy and progression of nephropathy at later stages were also associated with the long-term blood pressure levels. However, HbA1c levels were not associated with morbidity and mortality in cardiovascular disease or development of renal insufficiency.

Adult↗

PubMed1997

Artery blood pressure oscillation after active standing up: an indicator of sympathetic function in diabetic patients.

Dynamic artery blood pressure (Finapres) response to active standing up, normally consisting of initial rise, fall and recovery above the baseline (overshoot), was compared with the early steady-state artery blood pressure level to measure sympathetic vasomotor function in healthy subjects (n = 23, age 35 +/- 9 years; mean +/-SD) and in type I diabetic patients without autonomic neuropathy (AN) (group 1: n = 18, 38 +/- 13 years), with AN but no cardiovascular drugs (group 2a: n = 7, 44 +/- 11 years) and with both AN and cardiovascular drugs (group 2b: n = 10, 47 +/- 7 years). Systolic and diastolic overshoot were similar in the control (15 +/- 13/15 +/- 11 mmHg) and group 1 subjects. Systolic overshoot disappeared in 57% of patients in group 2a (-1 +/- 9 mmHg; P < 0.03), whereas artery blood pressure still overshot in diastole (8 +/- 7 mmHg; NS). Systolic overshoot disappeared in all patients in group 2b (-22 +/- 22 mmHg; P < 0.0006) and diastolic overshoot disappeared in 60% of these patients (-6 +/- 16 mmHg; P = 0.0006). Systolic early steady-state level was not lower in group 2a than in group 1 (NS), but it was impaired in group 2b (P < 0.006), in which six diabetic patients had a pathological response beyond the age-related reference values. There was a strong association between the overshoot and steady-state levels (P for chi 2 < 0.001, n = 58). Overshoot of the control subjects and patients in group 2b correlated to their respective steady-state blood pressure levels (r > or = 0.76; P < or = 0.001). In conclusion, baroreceptor reflex-dependent overshoot of the artery blood pressure after active standing up diminishes with the development of AN and it is associated with the early steady-state level of the artery blood pressure.

Adult↗

PubMed1997

The association between diabetic nephropathy and autonomic nerve function in type 1 diabetic patients.

Diabetic cardiovascular autonomic neuropathy increases the risk of deterioration in renal function and is associated with increased mortality in patients with renal failure. Type 1 diabetic patients with long diabetes duration, matched for age (38 +/- 9 years) and diabetes duration (28 +/- 8 years) were studied regarding the association between cardiovascular autonomic nerve function and different degrees of diabetic nephropathy. Eighteen patients were normo- (< 30 mg/l), six micro- (30-300 mg/l), and 13 macroalbuminuric (> 300 mg/l) based on urinary albumin concentrations in three separate morning samples. They were compared with 33 control subjects with similar age. Autonomic nerve function was evaluated by measuring the response of heart rate to deep breathing and active standing. Beat-to-beat finger artery blood pressure (Finapres) was tested during active standing. During deep breathing both change in heart rate (17 +/- 11, 9 +/- 7 and 4 +/- 3 beats/min) and ratio between expiratory and inspiratory R-R intervals (1.32 +/- 0.24, 1.14 +/- 0.15 and 1.05 +/- 0.04) decreased from normo- over micro- to macroalbuminuria (p < 0.05 vs normoalbuminuric and control subjects [17 +/- 5 beats/min and 1.28 +/- 0.10, respectively]). Similar results were obtained during active standing with respect to change in systolic arterial blood pressure (3 +/- 8, 2 +/- 13 and -6 +/- 11 mmHg; p < 0.05 vs control subjects [8 +/- 11 mmHg]). However, the response of diastolic arterial blood pressure or mean heart rate to standing up did not differ between any of the groups. The ratio of maximum to minimum R-R interval during the dynamic response of heart rate to active standing decreased with the degree of nephropathy (1.27 +/- 0.17, 1.11 +/- 0.11 and 1.05 +/- 0.06) with significantly higher values in patients with normo- compared with patients with macroalbuminuria (p < 0.05). All patients groups had significantly lower values than control subjects (1.46 +/- 0.22, p < 0.05). The overshoot of the blood pressure after an initial fall during active standing decreased with the degree of diabetic nephropathy. In conclusion, type 1 diabetic patients with long duration of diabetes have signs of cardiovascular autonomic neuropathy, the severity of which is related to the degree of nephropathy.

Adult↗

PubMed1997

Retinal examination intervals in diabetic patients on diet treatment only.

PURPOSE: The aim of the present study was to examine whether type 2 diabetic patients with good metabolic control achieved on diet treatment only, developed sight-threatening retinopathy during a four-year follow-up period. METHODS: A retrospective four-year follow-up study was carried out including all diabetic patients on diet treatment only, registered at the out-patient clinic at the Department of Medicine and referred for fundus photography to the Department of Ophthalmology in 1989 as well as all patients referred from primary care units for fundus photography during 1988 and 1989. One hundred and seventeen diabetic patients treated with diet only were examined with fundus photography after remittance, and after two and four years. RESULTS: Age at diabetes diagnosis was 58.8 +/- 13.8 years (mean +/- SD), age at baseline was 61.5 +/- 13.6 years, and diabetes duration was 2.7 +/- 3.1 years. During the four-year follow-up period, 48 of the patients (41%) remained on diet treatment only whereas diabetes treatment was changed in 66 (56%), from diet to oral agents only in 57 (49%), and from diet to insulin alone or in combination with oral agents in 9 (8%) of the patients. One hundred and six patients (91%) did not have any retinopathy at baseline and 11 patients (9%) had minimal background retinopathy. At follow-up, there were no signs of retinopathy in 93 patients (79%), 22 (19%) had minimal background retinopathy, and two had developed moderate background retinopathy. Out of those patients who were still on diet at follow-up, five (10%) had developed minimal background retinopathy. Mean blood glucose and HbA1c levels, registered every year during the observation period, were higher at most time points in patients who received oral agents or insulin treatment compared to those who were treated with diet only during the entire observation period. No differences were observed between patients who received oral agents and those who received insulin alone or in combination with oral agents. CONCLUSION: It is suggested, that if the initial retinal examination reveals no or minimal diabetic retinopathy at the time of diagnosis of type 2 diabetes mellitus, the second examination can be postponed at least 4 years in patients with good metabolic control on diet treatment only.

Aged↗

PubMed1997

Poor metabolic control, early age at onset, and marginal folate deficiency are associated with increasing levels of plasma homocysteine in insulin-dependent diabetes mellitus. A five-year follow-up study.

In a previous study, we showed that diabetic patients exhibited significantly increased concentrations of total plasma homocysteine (tHcy), but not until the onset of nephropathy. It was suggested that the hyperhomocysteinaemia might contribute to the accelerated atherosclerotic process in diabetic patients. In the present study, we have analysed the main determinants of plasma homocysteine (i.e. serum cobalamin, blood folate and serum creatinine), and also some other parameters related to diabetes mellitus, such as medical history, metabolic and renal quantities, on two occasions with a 5-year interval in 50 patients with insulin-dependent diabetes mellitus, in order to further elucidate the relation between plasma tHcy and diabetes mellitus. The result of the present study shows that diabetic patients with the lowest age at onset and with the poorest metabolic control are those most prone to a rapid increase in plasma tHcy concentration. The increment in plasma tHcy concentration in this group of patients may at least partly be explained by a marginal deficiency of blood folate concentrations.

Adult↗

PubMed1997

Lack of association between cystopathy and progression of diabetic nephropathy in insulin-dependent diabetes mellitus.

Whether an association exists between cystopathy and progression of diabetic nephropathy has never been clarified. The aim of the present study was to measure the degree of cystopathy in relation to the rate of progression of diabetic nephropathy. To that end, 17 insulin-dependent diabetic patients with diabetic nephropathy but without voiding symptoms were investigated urodynamically. The median age of the patients was 45 years (range 27-67 years), diabetes duration 23 years (range 14-44 years) and the serum creatinine level was 162 mumol/L (median, range 65-449 mumol/L) at the time of the study. The progression rate of diabetic nephropathy was analysed retrospectively by measuring changes in yearly mean values of Log10 serum creatinine for a period of 13 years (3-15 years) before the investigation. The progression rate was 0.028 mumol/L/year (median). Patients with a progression rate above and below the median rate were considered to be rapid (n = 8) and slow (n = 9) progressors, respectively. More women than men had a rapid progression rate of nephropathy. Rapid progressors were found to have smaller volume or residual urine (90 vs 165 ml; p < 0.05), larger volume voided (440 vs 270 ml; p < 0.05), lower opening pressure (18 vs 48 cm H2O; p < 0.05) and lower pressure at maximum flow (37 vs 64 cm H2O; p < 0.05) compared to slow progressors. However, these variables were not related to the progression rate of nephropathy (MANOVA). Furthermore, these results should be interpreted with caution because of the natural gender differences in pressure conditions. In conclusion, rapid progression of diabetic nephropathy does not seem to be associated with dysfunction of the urinary bladder measured with cystometry and pressure flow.

Adult↗

PubMed1997

[Diabetes mellitus--current Swedish national guidelines].

In 1996, national guidelines for the care and treatment of patients with diabetes mellitus were drawn up by specialists, in collaboration with representatives of the patient organisation, diabetes nurses, the professional associations of various medical specialties and central authorities. The national programme is divides into three parts: summarised information for decision-makers, clinical guidelines and complete information for patients. The guidelines are designed to provide a basis for treatment programmes at the local level. Among other things, the national guidelines stress the importance of the diabetes nurse both in primary and tertiary care, and emphasise the need of regional centers providing access to information and education and promoting the development of treatment. Another important aspect is fostering the influence of patient organisations at the local level, in order for the guidelines to have an impact on the quality of care for the individual patient.

Cost of Illness↗

PubMed1996

Restitution of neurophysiological functions, performance, and subjective symptoms after moderate insulin-induced hypoglycaemia in non-diabetic men.

The restoration of cognitive function was studied in 10 healthy men aged 26 years (25.5 +/- 1.2 years; mean +/- SD) after insulin-induced hypoglycaemia (arterialized blood glucose 2.5 +/- 0.4 mmol l-1) for 62 +/- 8 min. Another group of six men participated in a single blind sham study for comparison. The hypoglycaemic event caused a significant increase (p = 0.006) in serum adrenaline levels. Ratings of adrenergically mediated symptoms increased during hypoglycaemia (p = 0.006), as did neuroglycopenic symptoms (p = 0.002), although neuroglycopenia ratings increased in both studies. During hypoglycaemia, P300 amplitudes in a relatively demanding visual search task decreased (p = 0.02), whereas easier tasks were unaffected. The amplitudes were restored after 40 min of normoglycaemia. Reaction time deteriorated after restoration of normoglycaemia, suggesting an effect of hypoglycaemia on learning. Thus, hypoglycaemia at a blood glucose level that is common among patients treated with insulin causes clear cognitive dysfunction, although restoration of the cognitive dysfunction to normal was fast.

Adult↗

PubMed1996

The effect of the non-ionic contrast medium iohexol on glomerular and tubular function in diabetic patients.

The effect of the non-ionic contrast medium iohexol (Omnipaque) on renal function was investigated in diabetic patients with signs of peripheral ischaemia. Forty-six patients, 70 +/- 11 years (mean +/- SD) old, age at diabetes diagnosis 53 +/- 17 years, and with varying degrees of diabetic nephropathy were studied before 1, 2, and 30 days after aortobifemoral arteriography. Serum creatinine, creatinine clearance, urinary excretion of immunoglobulin G, albumin collagen IV (NC1), kappa and lambda chains, alpha-1 microglobulin and Tamm-Horsfall protein were evaluated. Within 1 month before and 30 days after arteriography, the glomerular filtration rate was measured by clearance of iohexol. The acute effect of the radiocontrast medium was an increase in the serum creatinine level in 41 (89%) patients, with a more than 25% increase in 12 (26%) patients. The excretion rates of immunoglobulin G and albumin decreased, whereas the proximal and distal tubular function and the excretion of collagen IV did not change. The increment in serum creatinine was associated with the preangiographic renal function (p < 0.05), a history of heart failure (p < 0.01), but not with age, duration and type of diabetes, gender, systolic or diastolic blood pressure, glycated haemoglobin (HbAlc) or blood glucose levels. The increase of serum creatinine was associated with a pre-existing proximal tubular dysfunction and a worsening of distal tubular function. No changes in the parameters measured persisted 30 days after angiography. In summary, a transient increment in serum creatinine level after arteriography occurred in 89% of diabetic patients. It was associated with the preangiographic renal function, a history of heart failure and signs of preexisting proximal tubular dysfunction and worsening of distal tubular function. However, these changes were reversible.

Age of Onset↗

PubMed1996

Retinal nitro blue tetrazolium staining and catalase activity in rat models of diabetes.

BACKGROUND: Recent studies have suggested that reactive oxygen species may be involved in the development of diabetic retinopathy. METHODS: Nitro blue tetrazolium (NBT) staining, a marker of reductants which may be induced by free radicals such as superoxide, and catalase activity, as an indirect measure of hydrogen peroxide (H2O2) generation, were studied in the rat retina in three conditions known to cause diabetes-like retinopathy, i.e. rats with spontaneous diabetes (the BB Wistar rat), rats with streptozotocin-induced diabetes mellitus, and rats fed on galactose. Male Wistar BB rats were studied 4-10 weeks after diagnosis of diabetes. Streptozotocin (60 mg/kg) was injected i.p. at 8 weeks of age and the experiments were performed after 8 weeks of diabetes. Young Sprague-Dawley rats were fed a 50% galactose diet for 9, 12 or 22 months. RESULTS: In trypsinized vessel preparations, more intense NBT staining was observed only in rats fed a galactose diet for 22 months. In cross sections, the number of stained vessels were increased in BB rats (p < 0.01), but not in rats with streptozotocin-induced diabetes. Catalase activity did not differ between any of the experimental groups and their matched controls. CONCLUSIONS: Increased amount of NBT reductants in retinal vessels occurred in BB Wistar rats and to some extent in galactose-fed rats, indicating a possible role for free radicals in the development of diabetic retinopathy. There was no evidence of increased retinal H2O2 production or activation of catalase, indicating that this particular enzyme was not affected during the conditions studied.

Animals↗

PubMed1996

HLA-DQB1*0201/0302 is associated with severe retinopathy in patients with IDDM.

Some insulin-dependent diabetic (IDDM) patients develop severe forms of retinopathy. Putative risk factors such as hypertension, poor metabolic control, nephropathy and growth hormone levels do not fully explain the progress of retinopathy in these patients. It has been discussed whether there is a genetic marker, since some diabetic patients without any known predisposing risk factors develop severe retinopathy and others do not. In the present study, HLA-DR and DQ were compared in two patient groups with IDDM. One group consisted of patients with early-onset diabetes, with severe non-proliferative or proliferative retinopathy; the other group had no or only mild signs of retinopathy. High resolution HLA typing was carried out by polymerase chain reaction (PCR) and hybridization with allele specific probes. Alleles on the DR3-DQ2 haplotype, DRB1*0301, DQA1*0501 and DQB1*0201, were more frequent in patients with severe retinopathy. A difference was seen when combining certain alleles in the genotypes of DQA1*03/0501 (p > 0.05) and DQB1*0201/0302 (p < 0.01). The findings of the present study suggest that DQB1*0201/0302 is the strongest genetic marker for severe retinopathy and DRB1*0301/0401 only has a secondary influence when combined with this genotype. It seems as if IDDM patients who are positive for the genotype DR3-DQ2/DR4-DQ8 (DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0401 -DQA1*03-DQB1*0302) are at greater risk of developing severe retinopathy.

Adult↗

PubMed1996

The prognostic value of albuminuria for the development of cardiovascular disease and retinopathy: a 5-year follow-up of 451 patients with type 2 diabetes mellitus.

The aim of the present study was to evaluate the risk for vascular morbidity or death and retinopathy in relation to urinary albumin concentration. To that end, we performed a 5-year follow-up study of all type 2 diabetic patients attending the outpatient-clinic. A total of 444 (98.4%) out of 451 adult patients initially studied were evaluated for the degree of retinopathy and levels of HbA1c blood pressure, serum creatinine and urinary albumin. Vascular morbidity and causes of death were registered by one and the most severe event only. Forty-seven patients developed atherosclerotic vascular disease, i.e. myocardial infarction (n = 19), cerebrovascular disease (n = 20), or amputation (n = 8), and 42 died. The observed annual mortality rate was 22.1/1000 compared to an expected rate of 13.6/1000 for the general population with corresponding age and sex. Urinary albumin concentration was found to be a prognostic marker for the development of vascular disease and death in patients treated with insulin at baseline (P < 0.01), whereas this was not the case in patients treated with diet and/or oral agents at baseline. However, insulin treatment per se was not associated with an increased mortality or mortality or morbidity. Urinary albumin concentration was not correlated with incidence or progression of retinopathy regardless of type of diabetes treatment. In conclusion, this study showed that albuminuria was a prognostic factor for vascular morbidity and death in type 2 diabetic patients treated with insulin but not in patients treated with diet or oral agents. Furthermore, albuminuria was not a predictor for incidence or progression of retinopathy.

Adult↗

PubMed1996

Glucose levels and insulin secretion during a 75 g glucose challenge test in normal pregnancy.

OBJECTIVES: The aim of the study was to evaluate glucose levels and insulin secretion early in pregnancy and at a time when gestational diabetes mellitus frequently occurs in order to define reference values for glucose tolerance during pregnancy. The results were also related to maternal factors that might identify subjects at risk of developing gestational diabetes mellitus as well as foetal factors that might be a result of impaired glucose tolerance during pregnancy. DESIGN: A prospective study. SETTING: All Caucasian women attending one antenatal out-patient care unit were offered a 75 g oral glucose tolerance test at the 17th and 32nd week of gestation. SUBJECTS: A total of 586 consecutive pregnant women were included in the study. All 586 women were examined by repeated blood glucose measurements and 298 agreed to perform oral glucose tolerance tests as well. MAIN OUTCOME MEASURES: Venous whole blood glucose values were measured in the fasting state and in samples obtained 15, 30, 45, 60, 75, 90 and 120 min after oral intake of 75 g glucose. Serum insulin and C-peptide were also measured at these times. In all subjects, a random blood glucose sample was taken at the first visit, and thereafter at the 20th, 30th and 36th week of gestation. Information was also obtained from all subjects regarding body mass index, weight gain during pregnancy, smoking habits, family history of diabetes and hypertension, hypertension during pregnancy, past obstetric history, parity, and fetal outcome. RESULTS: The glucose tolerance was significantly impaired at the 32nd week of gestation compared with the 17th week of gestation. The mean +2SD 2 h glucose value during the oral glucose tolerance test at the 32nd week of gestation was 8.0 mmol L-1. Impaired glucose tolerance was characterised by increased insulin resistance, with a significant rise in serum insulin and C-peptide concentrations and in the insulin/glucose index during the oral glucose tolerance test at the 32nd week of gestation. Maternal factors associated with an impaired glucose tolerance were a family history of diabetes mellitus, smoking, a weight gain more than 18 kg during pregnancy, and glucosuria, while a family history of hypertension and hypertension present during pregnancy were not. Foetal factors that might be a result of impaired glucose tolerance during pregnancy, e.g. macrosomia and prematurity as well as complicated deliveries such as vacuum extraction/forceps or Caesarean section, all tended to be associated with higher blood glucose values. The same pattern was seen when the Apgar score was < 7. CONCLUSIONS: The results from this study show that the present cut-off values for diagnosis of gestational diabetes mellitus should be revised. Even if some maternal factors might indicate an increased risk for impaired glucose tolerance during pregnancy, they are probably not enough to detect women with gestational diabetes mellitus. Therefore, a screening programme for gestational diabetes should be considered.

Adult↗