Impaired microvascular hyperaemic response in children with diabetes mellitus.

Clinically detectable microvascular complications of diabetes are uncommon in children with diabetes especially in the prepubertal group. It is unclear whether subtle functional abnormalities of the microcirculation occur in children without evidence of clinical microangiopathy and in particular whether abnormalities can be demonstrated in children before puberty. The maximum hyperaemic response to direct local heating (44 degrees C) of the foot skin was measured by laser Doppler fluximetry in 50 diabetic and 50 non-diabetic children. An impaired hyperaemic response occurred in the diabetic children compared with control children (diabetic 1.25 (95% CI 1.13-1.37) V; control 1.74 (1.60-1.88) V; p less than 0.001) and was significantly related to duration of diabetes but not to long-term blood glucose control. The impaired response was also present in prepubertal diabetic children (diabetic 1.37 (1.16-1.58) V; control 1.89 (1.67-2.12) V; p less than 0.001). Systolic and diastolic blood pressure were significantly raised in the prepubertal diabetic children. These data suggest that a functional abnormality of the microcirculation occurs in children with diabetes in the absence of clinically detectable microangiopathy, and even before puberty.     

Influence of arterial hypertension on diabetic retinopathy

The influence of arterial hypertension on the prevalence of diabetic retinopathy was evaluated by a cross-sectional study in 882 diabetic patients of whom 337 were insulin-treated and 505 were non insulin-treated. Arterial hypertension was defined by blood pressure values higher than 160-90 mmHg. Retinopathy was considered to be present when at least 2 microaneurysms were observed at the posterior pole. When duration of the diabetes was taken into account the prevalence of retinopathy in hypertensive subjects (69%) was not significantly higher than in normotensive subjects (47%) among the insulin-treated patients. However among non insulin-treated patients retinopathy was significantly more frequent in hypertensive (39%), than in normotensive subjects (25%; p less than 0.05).     

Skin capillary circulation severely impaired in toes of patients with IDDM,with and without late diabetic complications

Summary We have recently shown that the skin microcirculation of toes is significantly impaired in patients with diabetes and peripheral vascular disease, and this may be one major reason why these patients are highly susceptible to developing skin ulcers. The aim of the present study was to investigate whether the skin microcirculation is impaired also in diabetic patients free from macroangiopathy. One foot in each of 20 patients with insulin-dependent diabetes was investigated: 10 patients with and 10 patients without late complications. All patients had normal arterial circulation of their lower extremities. Two groups of age- and sex-matched healthy subjects served as controls. The capillary blood cell velocity in the nailfold of the great toe was investigated by computerised videophotometric capillaroscopy, and the total microcirculation within the same area evaluated by laser Doppler fluxmetry. The capillary blood cell velocity and the total skin microcirculation were studied during rest, and during postocclusive reactive hyperaemia. The total microcirculation was similar in patients and control subjects, whereas the capillary circulation was markedly reduced (p<0.01) in the patients. The ratio between the capillary and total microcirculation was significantly decreased (p<0.05–0.01) in the patients as compared to the control subjects, indicating a local maldistribution of blood in the skin microcirculation of the diabetic patients. The results of the present study show that in spite of a normal total skin microcirculation in the toes of insulin-dependent diabetic patients, both with and without late complications, the nutritional capillary circulation is severely impaired. These findings indicate that a chronic ischaemia is present in the skin capillaries of diabetic feet, and is related to the diabetic disease per se and not to late diabetic complications, and may be a cause for these complications.Abbreviations PVD Peripheral vascular disease - IDDM insulin-dependent diabetes mellitus - CBV capillary blood cell velocity - LDF laser Doppler fluxmetry     

Self-collection by diabetic patients of capillary blood for free insulin monitoring; reduction by diamide of haemolysis-induced insulin loss.

The need to precipitate bound insulin immediately after withdrawal of blood and the tendency to haemolysis, which reduces immunoassayable insulin, have prevented development of methods of self-collection of capillary blood for later free insulin measurement. We therefore investigated the use of the thiol-oxidizing agent, diamide, to prevent insulin loss with haemolysis and developed a self-collection procedure with capillary tubes pre-filled with diamide and polyethyleneglycol (PEG, for separation of free and bound insulin). Diamide (final concentration 5 mmol l-1) reduced serum insulin loss from 48 +/- 4 (+/- SE) to 11 +/- 4% (p less than 0.001) in maximally-haemolysed samples. The effect of diamide was concentration-dependent up to 5 mmol l-1. Diamide had no effect on the standard curve for radioimmunoassay of insulin. Levels of serum free insulin in self-collected capillary blood were significantly correlated with venous serum free insulin in 22 non-diabetic subjects (r = 0.92, p less than 0.001), 52 Type 1 diabetic patients (r = 0.86, p less than 0.001), and 18 Type 2 diabetic patients (r = 0.97, p less than 0.001). Mean capillary free insulin concentration was higher than in venous serum (22% in normal subjects, 64% in Type 1, and 23% in Type 2 diabetic patients). Storage at room temperature of capillary blood containing PEG/diamide for 72 h did not alter immunoassayable insulin concentrations.     

Blood pressure and microvascular complications in type 1 (insulin dependent) diabetic patients without hypertension

To specify the influence of blood pressure on diabetic microangiopathy, the factors related to retinopathy and nephropathy were studied among 56 consecutive type 1 (insulin-dependent) diabetic out-patients without hypertension. Diabetes mellitus had been diagnosed for at least one year (mean duration of diabetes +/- SEM = 11.4 +/- 0.9 years). Diabetic patients did not take any treatment liable to influence blood pressure. Clinical parameters, including blood pressure, tobacco and alcohol consumption, were recorded by the same investigator. Retinopathy was defined as more than 5 microaneurysms on a fluorescein angiogram, clinical and incipient nephropathy as an albumin excretion rate over than 300 mg/d and between 30 and 300 mg/d, respectively. On average, retinopathy (n = 25) was associated with longer duration of diabetes (16.5 +/- 1.2 vs 7.4 +/- 0.9 years; p less than 0.001) and higher systolic blood pressure (136.2 +/- 4.1 vs 126.3 +/- 2.8 mm Hg; p less than 0.05). Clinical (n = 9) and incipient (n = 23) nephropathies were associated with duration of diabetes (17.9 +/- 2.0 and 11.8 +/- 1.7 vs 8.7 +/- 1.6 years, respectively; p less than 0.01), and with systolic (145.0 +/- 7.9, 132.7 +/- 4.7 vs 123.5 +/- 4.2 mm Hg; p less than 0.01) and diastolic blood pressure (83.3 +/- 6.2, 77.3 +/- 3.2 vs 72.2 +/- 3.4 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Nailfold capillary microscopy can suggest pulmonary disease activity in systemic sclerosis

OBJECTIVE: To evaluate the association of capillaroscopic alterations with pulmonary disease activity in systemic sclerosis (SSc). METHODS: Ninety-one patients with SSc were studied by means of interview, physical examination, nailfold capillary microscopy (NCM), serology, pulmonary function tests, esophageal transit scintigraphy, Doppler echocardiography, and pulmonary high resolution computed tomography (HRCT). Pulmonary disease activity was diagnosed by the observation of ground-glass opacities on pulmonary HRCT. Capillary loss on NCM was evaluated using the avascular score: patients with mean score > or = 1 or mean number of megacapillaries per finger > or = 1 were considered to have severe capillaroscopic alterations. RESULTS: Patients with higher skin scores, longer disease duration, signs of peripheral ischemia, esophageal dysfunction, antitopoisomerase I antibodies, and ground-glass opacities had higher mean avascular scores (p < or = 0.05 in all tests). The association between ground-glass opacities and higher avascular scores was particularly strong in patients with disease duration < or = 5 years. Among these patients, ground-glass opacities were present in 14 of 19 patients with severe NCM alterations, but were absent in all patients (n = 8) with mild or no NCM alterations (p < 0.001). ROC curves confirmed the ability of NCM to discriminate between patients with and without ground-glass opacities among those with disease duration < or = 5 years. However, NCM could not predict the presence of reduced pulmonary diffusing capacity. CONCLUSION: The severity of NCM abnormalities is associated with lung disease activity in SSc, particularly when the disease duration is relatively short.     

Prevalence of diabetic retinopathy in children and adolescents with IDDM A population-based multicentre study

Summary Vision-threatening diabetic retinopathy can be prevented if it is diagnosed before becoming too advanced. Since diabetic retinopathy has been reported to occur only rarely before the end of pubertal development, children and adolescents are seldom included in screening programmes. We invited 780 children and adolescents with insulin-dependent diabetes mellitus diagnosed before the age of 15.0 years (disease duration of < 12 years) and who were older than 9.0 years at the time of examination from eight regions of Sweden. Retinal examination was performed with stereoscopic fundus photograph. The photograph were rated according to a modified Airlie House classification. The dropouts (223/780, 28.6 %) were significantly older and with a longer duration of diabetes than the examined children (p < 0.001 and 0.001, respectively). Photographs from 557 patients aged (median [interquartile range]:14.6 [12.4–17.0]) years and with a diabetes duration of 8.0 (5.5–9.9) years were evaluated. Retinopathy was demonstrated in 81 patients (14.5 %):66 with background retinopathy, 2 with microaneurysms and hard exudates, 12 with preproliferative retinopathy, 1 with proliferative retinopathy. Preproliferative retinopathy was diagnosed in a 12.8-year-old girl in pubertal stage 3 and an 11.8-year-old boy in pubertal stage 2, and proliferative retinopathy was found in a 21.5-year-old girl. Retinopathy was demonstrated in 6 % and 18 % of patients in pubertal stages 1 and 5, respectively. The overall prevalence of retinopathy in this population may even be higher since the dropouts were older and had a longer duration of diabetes. Since background and preproliferative retinopathy were found in children before puberty, we recommend including children and adolescents in screening programmes for diabetic retinopathy from the age of 10 years. [Diabetologia (1997) 40: 307–310] Received: 18 January 1996 and in revised form: 14 November 1996     

Sympathetic mediated vasomotion and skin capillary permeability in diabetic patients with peripheral neuropathy

AIMS/HYPOTHESIS: A loss of sympathetic function could lead to changes in capillary fluid filtration in diabetic patients. We investigated whether a decreased sympathetically mediated vasomotion in the skin in diabetic patients with peripheral neuropathy is associated with an abnormal capillary leakage. METHODS: Three matched groups were studied: 18 diabetic patients with documented peripheral neuropathy (DN), 18 diabetic patients without peripheral neuropathy (D), and 18 healthy control subjects (C). Sensory and motor nerve function of the distal extremities were assessed by standard neurography, and expressed in a sensory-motor nerve function score. Sympathetic vasomotion of the skin microcirculation was assessed by determining the power of blood flow variability in the low-frequency (0.02-0.14 Hz) band by spectral analysis of laser Doppler flowmetry at the median ankle. Skin capillary leakage was evaluated by sodium fluorescein videodensitometry at the same site of the foot. RESULTS: Sympathetically mediated vasomotion of the foot skin microcirculation was lower in diabetic patients with documented peripheral neuropathy compared with diabetic patients without peripheral neuropathy and control subjects (p<0.001). Capillary sodium fluorescein leakage was larger in 18 diabetic patients with documented peripheral neuropathy than in diabetic patients without peripheral neuropathy (p<0.02) and C (p<0.005). Multiple regression analysis disclosed that a reduced sympathetically mediated vasomotion, together with a lower sensory-motor nerve function score, independently contributed to the variance in sodium fluorescein leakage, for 30% (p<0.001) and 17% (p<0.01), respectively. CONCLUSIONS: A loss of sympathetic tone, apart from sensory-motor nerve dysfunction, seems to be a major determinant of an increased capillary permeability in diabetic patients with neuropathy.     

Osteopenia and metatarsal fractures in diabetic neuropathy

Radiographs of the hands and feet of 19 diabetic patients with severe neuropathy were compared to those of 22 control patients without neuropathy. The two groups were matched for age, sex, and duration of diabetes. Cortical bone mass, measured by x-ray morphometry, was significantly lower in both the hands (p less than 0.002) and the feet (p less than 0.001) of those with neuropathy. The osteopenia was worse in the feet than the hands and also worse in women. Serum alkaline phosphatase levels were also significantly higher in the neuropathy group (p less than 0.005). Metatarsal fractures were a frequent finding in the neuropathic patients, but were not seen in controls. The presence of metatarsal fractures was strongly associated with the subsequent development of diabetic osteopathy (p less than 0.001). We conclude that cortical bone mass in the feet and hands is reduced in severe diabetic neuropathy. This may contribute to the predisposition to metatarsal fracture and diabetic osteopathy.     

The effect of aldose reductase inhibition with ponalrestat on the width of the capillary basement membrane in diabetes mellitus

There is evidence to suggest that hyperglycemia is required for the development of the microvascular complications of diabetes. However, the precise mechanism by which hyperglycemia might cause diabetic complications is not completely clear. One possibility is the increased activity of the polyol pathway. Capillary basement membrane thickness is a hallmark histological finding in diabetic microangiopathy. Previous studies in experimental models of diabetes have related the polyol pathway with the thickness of basement membrane in retinal capillaries. To study the effect of aldose reductase inhibition with ponalrestat on the width of the skeletal muscle capillary basement membrane in subjects with diabetes, we measured the capillary basement membrane width in 55 subjects with diabetes in a double masked, placebo controlled randomized trial over a period of 18 months. Twenty-nine patients received ponalrestat (two 300 mg tablets daily) and twenty-six received placebo tablets. The age, sex distribution, type and duration of diabetes were similar in both groups. The glycosylated hemoglobin remained at a constant level throughout the study in both groups. The baseline capillary basement membrane width of the ponalrestat group was 3134 +/- 146 A, it was 3074 +/- 226 A at month 12 and 2548 +/- 182 A at month 18 (P less than 0.001 vs baseline value). The placebo group also had a significant reduction in the width of the capillary basement membrane, from a baseline value of 3026 +/- 147 A to 2818 +/- 144 A at month 12 and 2618 +/- 156 A at month 18 (P less than 0.001 vs baseline value). There was no statistical difference in the capillary basement membrane width between the two groups at any time point.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impairment of skin capillary recruitment precedes chronic complications in patients with type 1 diabetes

Microvascular function in patients with type 1 diabetes without chronic complications was assessed using skin capillary recruitment during post-occlusive reactive hyperemia (PORH). Structural (maximal) capillary density was evaluated during venous occlusion. The study included 48 consecutive outpatients aged 26.3 +/- 10.8 years with type 1 diabetes (duration of 9.5 years) without chronic complications and 34 control subjects. Intravital capillary video-microscopy was used in the dynamic study of skin capillaries in the dorsum of the fingers and toes. Capillary recruitment during PORH (% increase in mean capillary density, MCD) was significantly higher in the controls than the patients in both the fingers (p < 0.001) and toes (p < 0.001). During venous occlusion, MCD increase was also higher in the controls than the patients in both the fingers (p < 0.05) and toes (p < 0.0001). In patients, no difference was found between MCD at baseline and after venous occlusion in the fingers but a decrease was observed in the toes (p < 0.001). It is concluded that skin capillary function is significantly impaired in both fingers and toes of patients with type 1 diabetes without chronic complications. Moreover, capillary density during venous occlusion did not increase in either extremity in the patients, suggesting that their capillaries at rest are already maximally recruited.     

Intravital detection of skin capillary aneurysms by videomicroscopy with indocyanine green in patients with progressive systemic sclerosis and related disorders

Conventional capillaroscopy and infrared fluorescence videomicroscopy with indocyanine green were performed at the nailfold in 12 healthy controls and 38 patients with microangiopathy due to systemic sclerosis or related disorders. Saccular aneurysms featuring head and neck (type 1) and aneurysmatic enlargements (type 2) were defined. Microaneurysms were located at the apex or near the apex of capillary loops and were significantly more common in patients than in controls (p less than 0.02 for type 1 and p less than 0.001 for type 2). Combination of the two lesions was found only in patients and appears to be a valuable new diagnostic sign for the presence of microangiopathy. In comparison with conventional capillaroscopy, about twice as many microaneurysms were detected by videomicroscopy with indocyanine green coupling almost completely to plasma proteins. The new technique allows visualization of capillary aneurysms even when filled only by plasma.     

A nation-wide cross-sectional study of urinary albumin excretion rate, arterial blood pressure and blood glucose control in Danish children with type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood

Nation-wide screening for microalbuminuria in Denmark was performed in 22 paediatric departments treating children with Type 1 diabetes. Over a period of 6 months 1020 children (less than or equal to 12 years) and adolescents (greater than 12 to 19 years) were screened (81% of total). Of these, 957 (94%) performed at least two timed overnight urine collections. In 209 non-diabetic subjects the upper 95% limit for normal albumin excretion rate (AER) was 20 micrograms min-1. Mean overnight AER was significantly (p less than 0.001) elevated in diabetic (3.0 x/divided by 2.3 (SD tolerance factor) micrograms min-1) and in non-diabetic (2.5 x/divided by 2.2 micrograms min-1) adolescents compared with diabetic (1.7 x/divided by 2.1 micrograms min-1) and non-diabetic (1.3 x/divided by 2.2 micrograms min-1) children. In the diabetic patients AER was positively correlated with the body surface area and age. Among the patients with Type 1 diabetes, 4.3% (18 males and 23 females) had AER greater than 20 to 150 micrograms min-1 (persistent microalbuminuria). A further 7 adolescents (0.7%) had overt proteinuria (greater than 150 micrograms min-1). Clinical data for the 41 diabetic patients with AER greater than 20 to 150 micrograms min-1 were compared with those for 569 diabetic adolescents with AER less than or equal to 20 micrograms min-1 and duration of diabetes more than 2 years. The group with AER greater than 20 to 150 micrograms min-1 had significantly higher mean age (16.5 years) than the group with AER less than or equal to 20 micrograms min-1 (15.0 years; p less than 0.001). Females with AER greater than 20 to 150 micrograms min-1 had significantly higher mean HbA1c level (10.8 +/- 1.9%) than those with AER less than or equal to 20 micrograms min-1 (9.8 +/- 1.9%, p less than 0.003); they also had impaired linear growth (standard deviation score -0.25 vs + 0.16; p = 0.003). These associations were not found in males. Mean body mass index (BMI) was significantly increased in both females (22.2 +/- 2.9 kg m-2) and males (20.8 +/- 2.7 kg m-2) with AER greater than 20 to 150 micrograms min-1, compared with diabetic patients with AER less than or equal to 20 micrograms min-1 (females 20.8 +/- 3.0 kg m-2, p = 0.02; males 19.7 +/- 2.4 kg m-2, p less than 0.006).(ABSTRACT TRUNCATED AT 400 WORDS)     

Vital capillary microscopic findings in the nailfold of patients with diabetes mellitus

BACKGROUND: Preliminary investigation done in 100 healthy adults and 20 healthy children had shown that the interpretation of significance of changes in capillary morphology need to be corrected, since capillary changes previously considered to be pathological are also to be found in large numbers in healthy subjects. Against this background, the question has now been investigated whether the capillary microscopic findings in diabetics deviates from those found in normals, and whether the duration of the diabetes, its treatment, its sequelae, or concomitant diseases have any influence on the capillary microscopic appearance. PATIENTS AND METHODS: In 100 patients aged between 44 and 88 years with type 2 diabetes vital capillary microscopy was carried out on all ten fingers in the usual manner. The evaluation of the video recordings was done only when all the examinations had been completed--by two examiners blinded to the clinical data. RESULTS: It was shown that 66% of the patients demonstrated pathological capillary microscopic findings. These findings included pathologically increased apical and non-apical dilatations (32%), haemorrhagic extravasations (20%) and branchings (45%). No differences were found between the therapy groups (insulin--oral medication) nor was any relationship between the appearance of capillary changes and the duration of diabetes observed. Diabetics with concomitant diabetic sequelae (polyneuropathy), demonstrated no differences in capillary morphology as compared with diabetics with no such sequelae. CONCLUSION: Diabetics are found to have an increased incidence of pathological capillary morphology taking the form of increased apical dilatations, branchings and haemorrhagic extravasations. Neither the treatment, nor the duration of the illness, nor diabetic sequelae appeared to have any influence on the capillary microscopic changes.     

Association of glucose-6-phosphate dehydrogenase deficiency with diabetes mellitus

The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency was estimated in 318 diabetic patients using Beulter's fluorescent Spot test. A significantly (p less than 0.001) higher prevalence of G6PD deficiency was detected among diabetic patients (19.6%) as compared to controls (10.4%). The distribution of G6PD deficiency varied with age, sex, and duration of diabetes. Among diabetic men, the prevalence of deficiency was significantly higher than controls in both age groups; 40 years and below, and 41 years and above (p less than 0.005 and p less than 0.02, respectively). Among diabetic women, the significantly higher prevalence of deficiency was observed only in the young age group (p less than 0.005), whereas the difference among the older age group was not significant (p greater than 0.1). A significant increase in the prevalence of deficiency with increase in duration of diabetes was detected among men (p less than 0.05), but not in women. The results of the study suggest a positive association between G6PD deficiency and diabetes mellitus.     

The effect of the aldose reductase inhibitor, ponalrestat, on the progression of diabetic retinopathy.

The objective of this study was to evaluate the effects of ponalrestat, an aldose reductase inhibitor, on the progression of diabetic retinopathy. In this study, 62 patients with diabetes mellitus underwent a double-masked placebo-controlled clinical trial comparing the effect of ponalrestat 600 mg per day with a placebo on the progression of diabetic retinopathy. Both groups were comparable in terms of age, gender distribution, diabetes duration, metabolic control, and presence and severity of diabetic retinopathy. Seven-field stereo fundus photographs were performed at 0 (baseline), 12, and 18 months; 49 patients completed the study (26 in the ponalrestat group and 23 in the placebo group). In both treatment groups, a significant progression of diabetic retinopathy as evaluated by the Early Treatment Diabetic Retinopathy Study classification was observed (Wilcoxon Rank-Sum Test, p less than 0.05). No difference was observed in the progression of retinopathy between the two treatment groups (p = 0.96). The number of microaneurysms increased in the two study groups (from 5.6 +/- 1.2 to 10.5 +/- 1.3 in the placebo group and from 10.3 +/- 1.4 to 12.7 +/- 1.4 in the ponalrestat group); however, the increase was statistically significant only in the placebo group (p less than 0.05). When the increase in the number of microaneurysms was evaluated by change of category of microaneurysm count, no significant difference was observed. We conclude that ponalrestat at a dose of 600 mg per day has no clinically significant effect on the progression of diabetic retinopathy.     

Cross-section study of pulmonary function in patients with insulin-dependent diabetes mellitus

In this study, we attempted to establish the prevalence and nature of pulmonary dysfunction in a cross section of a diabetic population and the relationship of pulmonary dysfunction to diabetic factors and complications. Forty insulin-dependent diabetic patients, 15 to 60 yr of age, and 40 healthy reference subjects, matched for age, sex, and race, were studied. All subjects were lifelong nonsmokers and had no clinical evidence of past or present respiratory disease. Lung function was assessed from the flow-volume curve, single-breath nitrogen washout, static lung elastic recoil, and pulmonary diffusing capacity (DLCO/VA) and its components: membrane diffusing capacity (Dm/VA) and pulmonary capillary blood volume (Qc/VA). The diabetic patients had an increased value for Kst(L) and in Kst(L), the exponential shape constant of the pressure-volume curve compared with that of the reference subjects (Kst(L), 0.184 +/- 0.011 versus 0.135 +/- 0.005; p less than 0.005, mean +/- SEM). The DL/VA was lower in the diabetic subjects (4.62 = 0.12 versus 5.31 +/- 0.10 ml/min/mm Hg/L; p less than 0.001), and this was due to a lower Qc/VA (9.45 +/- 0.43 versus 11.75 +/- 0.35 ml/min; p less than 0.001). The Kst(L) and Qc/VA were correlated with the duration of diabetes. The In Kst(L) was negatively correlated with both DL/VA (r = -0.32, p less than 0.05) and Qc/VA (r = -0.36, p less than 0.05). There was no association between abnormal pulmonary function and the presence of other diabetic complications. It is concluded that there are mild, duration-related abnormalities of lung elastic recoil and pulmonary diffusing capacity and a reduction in pulmonary capillary blood volume in insulin-dependent diabetes mellitus.     

Putative risk factors associated with retinopathy in patients with diabetes diagnosed at or after 30 years of age

In a cross-sectional study of diabetic patients diagnosed at or after 30 years, and with different stages of retinopathy, factors such as duration of diabetes, treatment mode, metabolic control, blood pressure, and clinical signs of nephropathy were examined. The different stages of retinopathy used were absence of retinopathy, simplex, and severe retinopathy. Patients with simplex and severe retinopathy were older than those without retinopathy (p less than 0.001, and p less than 0.01, respectively). They also had a longer duration of diabetes (p less than 0.001), and were more often treated with insulin (p less than 0.001) and in larger doses (p less than 0.001). Their glycosylated haemoglobin levels were higher (p less than 0.01). Their systolic blood pressure was higher (p less than 0.01), but the diastolic blood pressure did not differ, and the number of patients treated for hypertension was similar in all groups. Albumin clearance was higher (p less than 0.01 and p less than 0.001), as were urinary albumin levels (p less than 0.001). The only variables that distinguished patients with simplex from those with severe retinopathy were albumin clearance (p less than 0.01) and urinary albumin levels (p less than 0.05).     

Limited joint mobility, Dupuytren's contracture and retinopathy in type 1 diabetes: association with cigarette smoking

To examine the associations between cigarette smoking, connective tissue changes, and diabetic retinopathy, a detailed smoking history was elicited from 150 normotensive non-diabetic subjects, and from 266 randomly selected adult patients with Type 1 diabetes, after examination for limited joint mobility, Dupuytren's contracture, and diabetic retinopathy. Mean insulin dose and current glycosylated haemoglobin concentrations were comparable in diabetic smokers and non-smokers. The historical duration of smoking correlated with the duration of diabetes (r = 0.72, p less than 0.001). In diabetic patients limited joint mobility was positively associated with retinopathy, being found in 73/147 (50%) patients with retinopathy compared with 20/114 (18%) without retinopathy (chi 2 = 28.9, p less than 0.001), and also with Dupuytren's contracture, 19/34 (56%) of patients with limited joint mobility having Dupuytren's contracture, compared with 76/232 (33%) of patients without Dupuytren's contracture (chi 2 = 7.05, p less than 0.01). Limited joint mobility was observed in 50% of diabetic smokers compared with 25% of non-smokers (odds ratio = 2.87 (corrected for diabetes duration), 95% confidence interval 1.64-5.01). Diabetic retinopathy was weakly associated with smoking (odds ratio 1.09; 95% confidence interval 0.60-1.96). There was however an increased prevalence of background retinopathy among male smokers (50% vs 29%; chi 2 = 6.88, p less than 0.01). In non-diabetic males limited joint mobility was observed in 37% of smokers but only in 11% of non-smokers (NS), while 33% of smokers and 8% of non-smokers had Dupuytren's contracture (p = 0.012). These results suggest that cigarette smoking contributes to the development of extra-articular connective tissue changes in both diabetic patients and non-diabetic subjects, and possibly to the development of diabetic retinopathy.     

Muscle capillary basement membrane in juvenile diabetes mellitus

Calculations of the minimum rather than the average basement membrane thickness of muscle capillaries established that widening of this structure was only rarely encountered in juvenile-onset diabetes of 1–6 yr duration. The basement membrane was usually, but not always, thickened, however, in childhood-onset diabetes present for 7 or more yr. The presence or absence of basement membrane thickening did not appear to be related to age at onset of diabetes, the degree of hyperglycemia in an oral glucose tolerance test, any residual ability to secrete insulin, the type, dosage or schedule of insulin therapy, history of ketoacidosis and shocking, blood pressure, or the state of the kidneys. However, each of the patients with an increase in the width of the basement membrane of muscle capillaries did have microaneurysms. Our data are consonant with the hypothesis that thickening of the basement membrane generally appears toward the end of the first decade following the diagnosis. Since duration and age tend to be related, such thickening was more common in the older persons with juvenile-onset diabetes. Also, in such patients serum creatinine tended to be higher and proteinuria was more frequent, two variables known to be influenced by duration of diabetes and increased chronologic age.