Elevated long-term glycated haemoglobin precedes proliferative retinopathy and nephropathy in Type 1 (insulin-dependent) diabetic patients

Summary The importance of glycaemic control for the development of proliferative retinopathy and nephropathy was assessed by monitoring glycated haemoglobin for 5 years or more before the diagnosis of these complications. The study comprised Type 1 (insulin-dependent) diabetic patients diagnosed at an age less than 31 years, and with diabetes duration 25 years or less. They were followed for an average of 7.9 years with 3.3 measurements per year. Of 172 patients screened for retinopathy 60 had no retinopathy, 104 had background retinopathy, and 8 had proliferative retinopathy. The mean HbA_1c (95% confidence intervals) of the groups was 6.4% (6.2–6.7%), 7.3% (7.1–7.5%) and 8.9% (8.1–9.6%), respectively (p<0.0001); the mean duration of diabetes was 12, 18, and 17 years. Of 186 patients 7 had nephropathy (albuminuria>200 mg/l). Mean HbA_1c in patients without nephropathy was 7.0% (6.8–7.1%) and in patients with nephropathy 8.8% (7.8–9.9%,p<0.001). Mean diabetes duration was 16 years in both groups. Multiple logistic regression including mean HbA₁₀, age at onset, duration, sex, and hypertension, was for both proliferative retinopathy and nephropathy significant only for mean HbA_1c. In all cases, proliferative retinopathy and nephropathy were preceded by poor glycaemic control over several years, suggesting that these complications are caused by poor glycaemic control.     

Early selective neuroretinal disorder in prepubertal type 1 (insulin-dependent) diabetic children without microvascular abnormalities

The duration of diabetes before puberty is not considered relevant to the future development of complications. To evaluate the effects of diabetes on the neural retina, we analysed macular function by steady-state focal electroretinography in 20 prepubescent diabetic children without vascular retinopathy and in 39 sex- and age-matched normal children. The mean (±SD) response related to retinal cellular elements between the photoreceptors and ganglion cells was significantly lower in diabetic children than in the control group (0.38±0.12 vs. 0.51±0.13 V; unpairedt-test=3;P=0.005). Similarly, ganglion cell function showed a significant impairment in diabetic children with respect to the control group (0.4±0.13 vs. 0.53±0.09 V; unpairedt-test=5.4;P=0.0001), whereas the photoreceptors appeared unaffected. Metabolic control and disease duration were not correlated with functional deficits. Our results suggest that before puberty, early diabetes may have a selective effect on the neural retina prior to the appearance of microvascular changes. A focal electroretinogram could identify diabetic children with neurosensory disorders who may have a higher risk of developing microvascular retinopathy.     

von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion

Summary High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A;n=9) or presence (Group B;n=8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123 %, 164 vs 132% and 159 vs 130 % (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9 % and +5 vs +1 % (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150±30 vs 130±12 mmHg,p=0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration. These data do not support the hypothesis that increases in plasma von Willebrand factor concentration reflect retinal endothelial injury in Type 1 diabetic patients with normal urinary albumin excretion. In these patients, high or increasing plasma von Willebrand factor levels may be related to systolic blood pressure.     

Effect of antihypertensive treatment on blood-retinal barrier permeability to fluorescein in hypertensive Type 1 (insulin-dependent) diabetic patients with background retinopathy

Summary The effect of antihypertensive treatment on blood-retinal barrier leakage of fluorescein in background retinopathy was studied in nine hypertensive Type 1 (insulin-dependent) diabetic patients suffering from nephropathy. The patients were investigated before and after 7 (3 to 13) months of treatment with captopril (n=8; 25 to 100 mg daily) and a diuretic, either frusemide (n=4; 80 to 200 mg daily) or bendrofluazide (n=2; 2.5 mg daily). Retinal function was assessed by fundus photography, fluorescein angiography, vitreous fluorometry, and renal function by glomerular filtration rate, and albuminuria. The antihypertensive treatment induced a significant reduction (p<0.05) in: blood pressure from 152/97±14/8 mmHg to 134/82±11/6 mmHg; blood-retinal barrier leakage of fluorescein from 2.4 ±1.1 to 1.4±0.5·10^–7 cm/second; albuminuria from 1391 (range: 168–4852) g/min to 793 (range: 35–2081) ug/min. Glomerular filtration rate declined from 88±15 to 78±23 ml·min^–1·1.73 m² (0.05<p<0.10). The metabolic control of the patients as reflected by their blood glucose and HbA_1c levels remained stable during the study. Our study suggests that systemic blood pressure elevation contributes to the abnormal blood-retinal barrier permeability to fluorescein characteristically found in diabetic background retinopathy and that this abnormality can be reversed during antihypertensive treatment.     

‘Microalbuminuria’ in type I (insulin-dependent) diabetic patients with and without retinopathy

Summary We investigated the frequency of microalbuminuria (albumin excretion rate, AER>15 μg/min) (‘overnight’ urine collection and radioimmunological evaluation) and its relation to retinopathy (assessed by fluorangiography) in 113 type I (insulin-dependent) diabetic subjects (aged 31±13 years; diabetes duration 11±7 years), all Albustix-negative. Sixty eight patients (60.2%) were free of retinal lesions, 31 (27.4%) had background retinopathy and 14 (12.4%) had proliferative retinopathy. Microalbuminuria was found in 25 patients (22%). Fifteen patients (13%) showed both retinopathy and microalbuminuria. Fifteen % (10/68) of the patients with no retinopathy and sixteen % (5/31) of those with background retinal lesions had microalbuminuria, while 29% (4/14) of the patients with proliferative retinopathy were normoalbuminuric. Among the 29 patients with diabetes for less than five years, 1 had retinopathy and 4 had microalbuminuria. Out of 15 patients with both retinopathy and microalbuminuria, 13 (87%) had had diabetes for more than 10 years. Diabetic retinopathy is more frequent than microalbuminuria (40vs 22%). Although the linkage between retinopathy and microalbuminuria is weak, after ten years of diabetes the two complications may frequently coincide. This work was performed within the context of theRicerca Finalizzata della Regione Toscana. In addition, it was supported in part by grant n ^o 84.02442.56 from the National Research Council and by a grant from theMinistero della Pubblica Istruzione (Ricerca Scientifica 1986).     

Erythrocyte sodium-lithium countertransport is not different in Type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy

Summary We studied erythrocyte sodium-lithium countertransport in 33 patients with Type 1 (insulin-dependent) diabetes mellitus with diabetic nephropathy, 18 patients with Type 1 diabetes without diabetic nephropathy and in 42 nondiabetic patients with various other renal diseases. No significant differences were found in sodium-lithium countertransport between these three groups (median (range) 322 (162–676) vs 321 (189–627) vs 300 (142–655) mol·1 cells^–1·h^–1). We conclude, that sodium-lithium countertransport cannot be used as a marker for diabetic nephropathy.     

Cigarette-smoking as a risk factor for macroproteinuria and proliferative retinopathy in Type I (insulin-dependent) diabetes

Summary In a case control study 192 cigarette-smoking patients with Type 1 (insulin-dependent) diabetes were compared with 192 non-cigarette-smoking patients pair-matched for sex (90 females), duration of diabetes (mean 14 years), and age (mean 32 years). Macroproteinuria was found in 19.3% of the smoking and in 8.3% of the non-smoking patients (p < 0.001). Proliferative retinopathy was present in 12.5% of the smoking and in 6.8% of the non-smoking patients (p < 0.025). The percentages of patients with normal proteinuria or without retinopathy were comparable between the two groups. In addition, glycosylated haemoglobin values and the prevalence of hypertension were similar between smoking and non-smoking patients. Thus, cigarette-smoking appears to be a risk factor for the progression of incipient to overt nephropathy and of background to proliferative retinopathy in Type 1 diabetes.     

Size- and charge selectivity of glomerular filtration in Type 1 (insulin-dependent) diabetic patients with and without albuminuria

Summary Albuminuria is the first clinical event in the development of diabetic nephropathy. We assessed glomerular charge- and size selectivity in 51 patients with Type 1 (insulin-dependent) diabetes mellitus of juvenile onset and 11 healthy individuals. Patients were allocated to five groups. The urinary albumin excretion rate was normal in group D1; 30–100 mg/24 h in group D2; 101–300 mg/24 h in group D3 and greater than 300 mg/24 h in groups D4 and D5. Group D5 had elevated serum creatinine (above 110 mol/l). Glomerular filtration rate and renal plasma flow were determined by constant infusion techniques and tubular protein reabsorption by excretion of 2-microglobulin. Charge selectivity was estimated from the IgG/IgG4 selectivity index. Size selectivity was measured by dextran clearance. Dextran was measured by refractive index detection after fractionation (2 Å fractions in the range 26–64 Å) by size exclusion chromatography. IgG/IgG4 selectivity index was significantly decreased in patients with albuminuria (p<0.001). The drop in IgG/IgG4 selectivity index was found in patients with minimal albuminuria (D2) and was not accompanied by any changes in tubular function or glomerular haemodynamics. Size selectivity was significantly altered only in patients with the most advanced nephropathy (D5) as reflected by an increase in the clearance of 62 Å dextran (p<0.04). We conclude that loss of glomerular charge selectivity precedes or accompanies the formation of new glomerular macromolecular pathways in the development of diabetic nephropathy.     

Kidney transplantation in Type 1 (insulin-dependent) diabetic patients

Summary The development of diabetic glomerulopathy in kidneys transplanted to diabetic patients was estimated in transplant biopsies and evaluated in relation to suspected clinical risk factors for diabetic nephropathy. Surgical biopsies were taken at baseline and at 24–36 months post-transplantation in 16 Type 1 (insulin-dependent) diabetic patients and 8 non-diabetic control subjects with a glomerular filtration rate more than 30 ml·min^– at follow-up. Immunosuppressive therapy included cyclosporine in all but one case. Stereological methods were used to assess basement membrane thickness, volume fraction of mesangium per glomerulus, and volume fraction of matrix per mesangium. The volume fraction of interstitial tissue per cortex was estimated by light microscopy. After 2 years the basement membrane thickness had increased by 55 nm (SD 58 nm) in the diabetic group. This change was significantly different from that of 2 nm (SD 37 nm) in control subjects (p=0.02). Mesangial volume fraction increased significantly by 0.04 (SD 0.03) in diabetic patients, and this change was significantly different from that of -0.01 (SD 0.04) in non-diabetic patients (p=0.009). No change was detectable in the matrix expressed as fraction of mesangial volume. An increase in interstitial volume fraction from baseline to 2 years was observed, but was significant only in the diabetic group (p=0.04). The changes in structural parameters did not correlate with mean values during follow-up of glycated haemoglobin or estimated protein intake, nor was any pattern discernible in the relationship to graft tissue types. The observed increase in basement membrane thickness corresponds to that observed in native kidneys during the first years of diabetes, whereas an increase in mesangial volume fraction — using a different protocol — was not observed in the early phase of the natural development. Absence of correlation with the various risk factors may reflect an irrelevance of these variables within the current range, or their influence may be offset by stronger mechanisms in the transplant situation, and therefore does not appear in this relatively small series.     

The number of glomeruli in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients

Summary The number of glomeruli per kidney in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients was estimated by an unbiased stereological method: the fractionator. No significant differences were observed between Type 1 and Type 2 diabetic patients without severe diabetic glomerulopathy and non-diabetic patients. Diabetic patients with proteinuria who were in the early stages of diabetic nephropathy also had a normal number of glomeruli. On the other hand, a subgroup classified as Type 1 diabetic patients with severe diabetic glomerulopathy had significantly less glomeruli compared with Type 1 diabetic patients with mild or no glomerulopathy. A probable explanation is that Type 1 diabetic patients lose glomeruli in relation to the progression of diabetic glomerulopathy. A more theoretical alternative is, however, that development of diabetic glomerulopathy is facilitated by a low number of glomeruli.Presented in part at the first meeting of the European Diabetic Nephropathy Study Group, Pisa, Italy, April 1988, and at the 23rd annual meeting of the Scandinavian Society for the Study of Diabetes, Bergen, Norway, May 1988     

Long-term treatment with fidarestat suppresses the development of diabetic retinopathy in STZ-induced diabetic rats

It is important to suppress retinal vascular changes for prevention of the onset and progression of diabetic retinopathy. In the present study, we investigated the dose–response effect of an aldose reductase (AR) inhibitor, fidarestat, on retinal vascular changes in the retinas of streptozotocin (STZ)-induced diabetic rats. Fidarestat (0.5, 1, and 2 mg/kg) was administered once a day, from 4 days after STZ injection, for 15 months. Microaneurysms and thickness of the basement membrane were frequently observed in the untreated diabetic group as compared to the nondiabetic control group. In addition, the number of pericytes decreased in the untreated diabetic group. Fidarestat diminished the prevalence rate of microaneurysms, basement membrane thickness and decrease in the number of pericytes, and complete suppression was observed at a dose of 2 mg/kg. Fidarestat also dose-dependently inhibited sorbitol accumulation in the retina. Furthermore, a close correlation was observed between the prevalence rate of microaneurysms and the decrease in the number of pericytes, which indicated that damage to pericytes triggers retinal vascular changes. These results suggest that fidarestat, by virtue of its long-term correction of the accelerated polyol pathway, has a potential role in preventing the progression of diabetic retinopathy.     

Visual symptomatology in patients with sight-threatening diabetic retinopathy.

AIMS: To assess the level of visual symptomatology in patients with sight-threatening diabetic retinopathy. METHODS: Questionnaires were completed by patients undergoing first photocoagulation treatment for diabetic maculopathy or proliferative retinopathy during a 2-month period throughout the UK, and at 9 months' follow-up. RESULTS: There were high levels of visual symptomatology prior to the first laser treatment and at follow-up for both patients with maculopathy or with proliferative retinopathy. Only 25.1% of patients with maculopathy and 17.2% of patients with proliferative retinopathy were asymptomatic in terms of reading, seeing the television screen, recognizing faces or with their night vision at baseline. For those with maculopathy 20.1% were aware of colour vision abnormality in the eye to be treated at baseline and 9.5% were aware of new central scotomata since the treatment. Of those with proliferative retinopathy, 13% said that they had given up driving due to poor eyesight and 19% were aware of new peripheral field defects since the treatment. CONCLUSIONS: There are high levels of visual symptomatology for patients with sight-threatening diabetic retinopathy in the UK despite that fact that screening should aim to detect retinopathy prior to visual loss occurring. Patients should be aware that there may not be any significant improvement in their vision with laser treatment, and that the main aim of treatment is to reduce the likelihood of further visual deterioration.     

Residual B-cell function in insulin-dependent (type I) diabetics with and without retinopathy

Summary In order to evaluate if residual B-cell function is a protecting factor against the development of diabetic retinopathy in type I diabetics we measured C-peptide levels before and after glucagon stimulation (1 mg i.v.) in 74 type I diabetics. In all patients retinopathy was assessed by fluorescein angiography and retinal lesions were classified as: grade 0, normal; grade 1, background retinopathy; grade 2, proliferative retinopathy. We then correlated the degree of retinopathy to sex, age, duration of diabetes, smoking, percentage of ideal body weight, systolic and diastolic blood pressure, serum cholesterol, triglycerides, creatinine and C-peptide by means of multiple linear regression analysis. Twenty-three out of 74 type I diabetics had retinopathy. In all 7 subjects with proliferative retinopathy duration of diabetes exceeded 10 years. There was significant correlation between retinopathy and duration of diabetes (r=0.373, p<0.001). No correlation was found between retinopathy and all the other variables, in particular between retinopathy and basal C-peptide or C-peptide increment (Δ). An inverse correlation was found between the increment of C-peptide and duration of diabetes (r=−0.404, p<0.01). Our data show that residual B-cell function cannot be considered a protecting factor against the development of diabetic retinopathy.     

Intercellular adhesion molecule-1 (ICAM-1) polymorphism is associated with diabetic retinopathy in Type 2 diabetes mellitus.

AIMS: Leucocyte adhesion to the diabetic retinal vasculature has been implicated in the pathogenesis of diabetic retinopathy. We evaluated the relationship between genetic polymorphisms in leucocyte and endothelial cell adhesion molecules and diabetic retinopathy in Type 2 diabetes mellitus. METHODS: We determined ICAM-1, platelet endothelial cell adhesion molecule-1 (PECAM-1), and leucocyte endothelial adhesion molecule-1 (LECAM-1) genotypes in 81 patients with and 50 without diabetic retinopathy. RESULTS: The frequency of ICAM-1 469KK genotype and K allele were significantly higher in the patients with diabetic retinopathy than in those without retinopathy (genotype 42% vs. 20%, chi2 = 6.70, P = 0.035; allele 66% vs. 50%, chi2 = 6.49, P = 0.011). With regard to the PECAM-1 V125L and LECAM-1 P213S polymorphisms, there were no significant associations between the distribution of genotypes or allele frequencies and the presence of diabetic retinopathy. Independent of other risk factors, the ICAM-1 469KK genotype was associated with a 3.51-fold increased risk for retinopathy. CONCLUSIONS: These data suggest that the ICAM-1 469KK genotype could be a genetic risk factor for retinopathy in Type 2 diabetes mellitus.     

A nationwide cross-sectional study of retinopathy and microalbuminuria in young Norwegian Type 1 (insulin-dependent) diabetic patients

Summary A nationwide cohort of Type 1 (insulin-dependent) diabetic patients was studied to determine the prevalence of retinopathy and microalbuminuria and to evaluate the association to various risk factors. Of 600 subjects with mean age of 19.8 years (range 8.0–30.3) and a mean duration of diabetes of 10.5 years (range 6.2–17.3),371 (60 %) volunteered for a clinical examination which included fundus photography, timed overnight urine samples for albumin excretion rate, measurement of arterial blood pressure and determination of HbA_1c, Retinopathy was found in 122 of 371 patients (32.8 %), in 3 of 41(7.3 %) patients aged less than 13 years. The youngest subject with retinopathy was 9.6 years old. Microalbuminuria was found in 44 of 351 patients (12.5 %), in 1 of 41(2.4 %) patients aged less than 13 years. The youngest subject with microalbuminuria was 11.5 years old. Mean HbA_1c was 8.6 % (normal range 4.5–6.1 %). Patients with retinopathy had significantly higher mean age (p = 0.0001), longer mean duration of diabetes (p = 0.0001), higher mean HbA_1c (p = 0.009), and higher mean arterial blood pressure (p = 0.0001) compared to patients without retinopathy. In microalbuminuric patients HbA_1c (p =0.0001) and mean arterial blood pressure (p = 0.01) were significantly higher compared to non-microal-buminuric patients, but there was no difference in age or diabetes duration. Ina multiple logistic regression model, age, HbA, duration of diabetes and mean arterial blood pressure were found to be significantly associated with retinopathy, while HbA_1c mean arterial blood pressure and onset before 13.0 years of age were found to be associated with microalbuminuria. The prevalence of retinopathy and microalbuminuria was relatively low. Both retinopathy and microalbuminuria were strongly associated with blood glucose control and developed at prepubertal age in some patients. The findings indicate that more intense optimization of blood glucose control in children and adolescents with Type 1 diabetes is warranted.     

Pulmonary complications of Type 1 (insulin-dependent) diabetic patients

Summary We have investigated the influence of diabetes mellitus including the presence of late complications on the pulmonary system. To check this relationship 31 Type 1 (insulin-dependent) diabetic patients (mean age 30.6±5.32 years, mean duration of diabetes 12.9±5.05 years) were admitted into the trial and compared with 18 control subjects. Pulmonary function tests were measured including spirometric parameters, diffusing capacity, specific diffusing capacity and dynamic compliance measured at 20 and 60 breaths per min. No disturbance of the spirometric parameters was observed in the diabetic patients. Diffusing capacity in the diabetic patients with complications was significantly lower than in both the diabetic patients without complications and the control group (81.2±16.2%, 104±13.7%, 99.3±2.8%; p<0.001, p<0.005 respectively). Specific diffusing capacity was significantly lower in the diabetic patients than in the control subjects (80.3±13.1% vs 89.4±12.9%; p<0.05). In the group with late complications specific diffusing capacity was lower than in the group without complications (69.7±9.17%; 87.2±10.7%, respectively; p<0.001). Dynamic compliance at 20 breaths per min in diabetic patients was 84.06±17.08% vs 95.2±11.59% in the control subjects (p<0.05). It was particularly low in the group with late complications 80.6±13.2% and patients with metabolic poor control, 80.3±12.02% (both p<0.005 vs the control group). Dynamic compliance at 60 breaths per min was 60.1±15.0% as compared to 83.2±13.3% in the control group (p<0.001). We conclude that the disturbances of dynamic compliance may be due to the local mosaic abnormalities of lung elasticity, caused by the non-enzymatic glycation of protein. Disturbances in diffusion in diabetic patients confirm the presence of microangiopathy in pulmonary vessels.     

Relationship between diabetic retinopathy and vascular endothelial function in elderly type 2 diabetic Japanese patients without cardiovascular disease

Background:   Many recent studies point to the importance, in diabetic patients, of vascular endothelial function as an early marker of not only macrovascular complications but also of microangiopathy. The aim of this study is to investigate the relationship between diabetic retinopathy and endothelial function in elderly diabetic patients by using brachial artery flow-mediated dilation (FMD).
Methods:   We studied 71 type 2 diabetic patients aged 65 years or older without cardiovascular diseases. The subjects were categorized as three groups: (i) without diabetic retinopathy ( n  = 49); (ii) with non-proliferative diabetic retinopathy group ( n  = 15); and (iii) those with preproliferative or proliferative diabetic retinopathy ( n  = 7). Brachial artery FMD measurement was performed by high-resolution ultrasonography. The Kruskal–Wallis test, the χ² test and multivariate logistic regression analysis were used to identify associations between both retinopathy and clinical characteristics and FMD.
Results:   There were no differences in clinical characteristics between the three groups. FMD of the three groups were significantly decreased correlating with the severity of retinopathy (8.03% vs 5.40% vs 2.30%; P  = 0.003). Multivariate logistic regression analysis showed that there was a significant correlation between diabetic retinopathy and FMD (odds ratio 0.801; P  = 0.009).
Conclusion:   Our study suggests that FMD has a relation to microangiopathy in elderly diabetic subjects. Prospective studies will be required to determine whether this test has any clinical use for identifying elderly diabetic patients who are likely to develop diabetic retinopathy.     

Circulating insulin-like growth factor I in Type 1 (insulin-dependent) diabetic patients with retinopathy

Summary The relationship between insulin-like growth factor I (IGF I) and diabetic retinopathy was investigated. This somatomedin circulates bound to at least two large carrier proteins with molecular weights of approximately 150,000 and 35,000. Total and protein binding profiles of insulin-like growth factor I were determined in the serum of 18 patients who had had Type 1 (insulin-dependent) diabetes for 15–20 years, but had no signs of nephropathy and a similar degree of mild subclinical neuropathy. Nine had preproliferative or proliferative retinopathy and 9 had little or no background retinopathy but there was no difference in diabetes duration, insulin doses or glycaemic control between the two groups. In the latter group, the amounts of the somatomedin I and the serum profiles were similar to those in 9 healthy control subjects. In patients with advanced retinopathy, however, binding of insulin-like growth factor I to the carrier proteins was significantly altered. Binding to the low molecular weight protein increased to 140% whereas binding to the large molecular weight protein decreased to 70% of the normal level. In the latter Type 1 diabetic patients total serum insulin-like growth factor I was decreased to 60% of the normal level (p<0.02). When the alteration in serum profile was adjusted for, the level of somatomedin associated with the small carrier complex was normal whereas that associated with the large carrier complex was reduced by almost 60% in Type 1 diabetic patients with retinopathy. It is proposed that the total circulating somatomedin level is low in advanced diabetic retinopathy. Furthermore, changes in. the carrier binding of insulin-like growth factor I rather than in the total circulating level of the somatomedin may be involved in diabetic retinopathy.     

Coronary heart disease in young Type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors

Summary Fifty-nine Type 1 (insulin-dependent) diabetic patients with (group I) and 59 patients without nephropathy (group II) pair-matched according to sex (30 males and 29 females), age (33 years, range 15–48) and diabetes duration (19 years, range 6–42) were followed for a period of 10 years from about 5 years before to 5 years after onset of proteinuria. The cumulative incidence of coronary heart disease was estimated, and blood pressure and serum cholesterol were followed. Within six years after onset of proteinuria the cumulative incidence of coronary heart disease was increased eight-fold in group I (40%) compared with group II (5%), (p<0.001). Blood pressure was higher in group I compared with group II from before onset of proteinuria (135/86±17/9 mmHg vs 129/80±15/8 mmHg, p<0.001), and serum cholesterol elevated from onset of proteinuria in group I (6.3±1.2 mmol/l) vs. group II (5.5±1.0 mmol/l), (p<0.005). Patients in group I who developed coronary heart disease had similar age (36 years, range 21–51, vs 38 years, range 21–53), sex (50% males vs. 52% males), smoking frequency (50% vs 49%), diabetes duration (22 years, range 9–39, vs 24 years, range 10–42) and serum creatinine (110 mol/l, range 69–284, vs 108 mol, range 72–1024) compared with patients not developing coronary heart disease. However, the patients with coronary heart disease had higher blood pressure (135/87mmHg±16/9 vs 128/82±15/7, p<0.05) and serum cholesterol (7.3 mmol/l+ 1.2 vs 6.4 mmol/l±0.9, p<0.05) than patients without coronary heart disease. Thus, patients developing clinical nephropathy have a highly increased incidence of coronary heart disease compared with patients not developing nephropathy. Patients who developed coronary heart disease were characterized by higher blood pressure and serum cholesterol.