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In type I diabetes, the quality of life and, in essence, the long-term prognosis or life expectancy of the patient are invariably related to the manifestation of untoward complications. Increased arterial blood pressure (hypertension) has a great influence in these complications. Cumulative evidence has shown that proteinuric type I diabetic patients are easily susceptible to hypertension and its accompanying sequelae. The debilitating effects of hypertension on the progressive development of diabetic nephropathy leading to renal dysfunction and mortality in renal transplant patients have been documented. Proliferative retinopathy and cardiovascular lesions are also frequent devastating complications in hypertensive-diabetic patients. The mechanism of sodium/lithium countertransport activity and the genetic predisposition to hypertension require further elucidation.
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PMID:Comments on the clinical impact of hypertension in type I diabetes. 147 46

The cardiovascular risk profile was assessed in all 208 diabetics accepted for dialysis in 28 German dialysis centres from 1985-1987 (104 men, 104 women, mean age 60 [22-82] years). 71 patients had type 1 and 128 type 2 diabetes, and 9 maturity onset diabetes of the young. Of 169 patients, 164 (97%) had hypertension (median systolic blood pressure at start of dialysis 200 [120-280] mm Hg). Only 74 patients (44%) were on continuing anti-hypertensive medication. Median serum cholesterol was 225 (66-424) mg/dl, LDL-cholesterol 158 (43-335) mg/dl and HDL-cholesterol 32 (10-67) mg/dl. In patients with a history of myocardial infarction (n = 26) the median cholesterol concentration was 269 (126-424) mg/dl, while in those with no history of myocardial infarction (n = 132) it was 221 (66-280) mg/dl (P less than 0.05). Only 5% of the patients had received lipid lowering therapy. Out of 175 patients, 65 (37%) had a history of smoking, and 25 (14%) were still smokers at the start of dialysis. There was a strong association between smoking history and amputations. Only 98 of 208 patients (47%) had had a specialist ophthalmological examination in the 12 months preceding the start of dialysis. Proliferative retinopathy was present in 33 out of 53 (62%) type 1 and 15 out of 98 (15%) type 2 diabetics. Out of 22 patients with unilateral or bilateral blindness, 2 (10%) had received no photocoagulation. - This investigation reveals a need for better medical care of diabetics with pre-end-stage renal failure.
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PMID:[Does the care of diabetic patients with renal failure in the predialysis phase need improvement?]. 191 32

The prevalence of microalbuminuria and persistent proteinuria was studied in a population of 801 diabetic patients (535 with type II and 266 with type I diabetes). Urinary albumin excretion rate (AER) was measured on morning samples by laser nephelometry. Normoalbuminuria, as defined, in the absence of contaminated urine, by an albumin: creatinine (A/C) ratio below 2, was found in 551 patients, microalbuminuria (NC greater than or equal to 2 with AER below 200 mg/l) in 190 patients and persistent proteinuria (AER greater than or equal to 200 mg/l) in 60 patients. Microalbuminuria was present in 48 (18 p. 100) IDDM patients and 142 NIDDM patients. In IDDM patients, AER increased with the duration of the disease with no apparent influence of age at the onset. The prevalence of hypertension was 25 p. 100 and 61 p. 100 in IDDM patients with microalbuminuria and macroproteinuria respectively versus 10 p. 100 in patients with normoalbuminuria. This prevalence increased in NIDDM patients from 39.3 p. 100 with normoalbuminuria to 40.8 p. 100 and 76.2 p. 100 with microalbuminuria or macroproteinuria respectively. Proliferative retinopathy in type I and type II patients with normal AER was 7.4 p. 100 and 1.2 p. 100 respectively increasing to 15.2 p. 100 and 8.9 p. 100 with microalbuminuria and 27.8 p. 100 and 23.1 p. 100 with macroproteinuria. The prevalence of coronary disease increased from 4 to 10.4 p. 100 in patients with type I diabetes and microalbuminuria. The prevalence of cardiac failure increased from 1.5 to 2.1 p. 100 in type I diabetics and from 3.2 to 7.8 p. 100 in type II diabetics in the presence of microalbuminuria. Patients with microalbuminuria had increased levels of glycosylated hemoglobin A 1C but statistical difference was only obtained for patients with type II diabetes. Routine analysis of AER in diabetics allows early detection of diabetic nephropathy and emphasizes the need for tight metabolic and blood pressure control. Hypertension can be detrimental to nephropathy but might also initiate renal lesions in NIDDM patients.
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PMID:[Microalbuminuria and diabetic nephropathy. Detection and correlation with other degenerative complications]. 214 8

Among 163 insulin-dependent (type I) diabetics (average age 43.5 years; average duration of diabetes 17.5 years), 40 (24.5%) died within ten years from the consequences of micro- and (or) macro-angiopathies. The death-rate among hypertensives was twice that among normotensives: 21 of 53 patients (39.6%) with blood pressures above 160/95 mmHg, but 19 of 110 patients (17.3%) with normal pressures. Proliferative retinopathy at the onset of the study was also a predictive marker of a poor prognosis. The death-rate increased threefold for patients with retinopathy if they also had hypertension: 13 of 30 (43.3%) with background retinopathy and hypertension died, compared with 9 of 68 without hypertension (13.2%; P less than 0.01). Independently of hypertension the death-rate for patients with persistent proteinuria (greater than 0.5 g/24 h) was about threefold that among those without it. The highest death-rate (56.7%) was among the 30 patients with proteinuria and hypertension. Stepwise linear regression analysis demonstrated that the correlation between death from micro- and macro-vascular disease and the known risk factors was entirely determined by blood pressure and proteinuria.
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PMID:[Significance of proteinuria and hypertension in the prognosis of type 1 diabetes. Results of a 10-year follow-up study on micro- and macrovascular disease mortality]. 276 53

Diabetic nephropathy develops in about 45% of insulin dependent diabetics of whom two-thirds will develop renal failure, the rest dying from cardiovascular disease. Most of the excess mortality of insulin dependent diabetics occurs in those with proteinuria. Among non-insulin dependent diabetics nephropathy is also an important cause of increased mortality but this is mainly from cardiovascular disease. Once diabetic nephropathy is established it progresses relentlessly to end-stage renal failure over about seven years, but ranging from five to 20 years. The explanation for the different rates of progression in individual patients is not understood. Hypertension accompanies diabetic nephropathy and its treatment may retard the progression of renal failure. Other forms of intervention include glycaemic control which has not been shown to have any effect, and protein restriction for which no conclusions can be drawn at present. The diagnosis of diabetic nephropathy is straightforward in the presence of a typical history and clinical features. Non-diabetic renal disease is sometimes the cause of renal failure and may require specific treatment; prognosis for renal failure treatment may be better than for nephropathy patients with other diabetic complications. Other diabetic complications develop as diabetic nephropathy progresses, most notably cardiac and peripheral vascular disease. Proliferative retinopathy and neuropathy are considerable problems and their management needs attention both before and after renal failure treatment.
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PMID:Clinical diabetic nephropathy: natural history and complications. 353

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 less than 0.001). Proliferative retinopathy was present in 12.5% of the smoking and in 6.8% of the non-smoking patients (p less than 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.
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PMID:Cigarette-smoking as a risk factor for macroproteinuria and proliferative retinopathy in type 1 (insulin-dependent) diabetes. 375 32

This paper reports on 9 patients aged 13-18 years (mean 15.4) with severe diabetic retinopathy. Two patients were prepubertal and 4 were going through puberty. Hypertension was present in 2 patients, while 4 had proteinuria. Severe preproliferative disease was present in 3 patients initially and proliferative retinopathy in the remainder. In 5 this retinopathy was considered to be florid. Two patients seen prior to 1975 had pituitary ablation, while those seen after 1975 were treated by extensive argon and xenon arc photocoagulation. Proliferative lesions regressed in both groups. At the latest follow-up 7 of the 9 patients achieved a final visual acuity of 6/9 or better in at least one eye. One patient became blind. Proliferative retinopathy advances rapidly in adolescents, but photocoagulation, as used now, can maintain vision in most.
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PMID:Severe diabetic retinopathy in adolescents. 668 87

This study analyzed the prevalence, aggravating factors (including duration of diabetes, glycemic control, body mass index, hypertension, serum total cholesterol, changes of ST on ECG and diabetic therapies) and characteristics of diabetic retinopathy in 75 patients with pancreatic diabetes resulting from calcifying pancreatitis. The patients were divided into three Groups: Group I (27 patients in whom diabetes was detected earlier than pancreatic stones), Group II (36 patients in whom diabetes and pancreatic stones were simultaneously detected) and Group III (12 patients in whom pancreatic stones were detected earlier than diabetes). The prevalence of retinopathy was dependent on the duration of diabetes as well as poor glycemic control. It was significantly (p < 0.01) higher among the patient with the duration of diabetes that was more than 5 years than that of the patients whose duration was less than 5 years. The prevalence of retinopathy in Group I (63%) was significantly (p < 0.05) higher than that in Group II (30.6%) and Group III (12.5%). Proliferative retinopathy was not found in any patients with a duration of diabetes less than 5 years, while it was found in 5 patients with a duration of more than 5 years (5 cases out of 31 patients). Diabetic retinopathy was correlated with the duration of diabetes and glycemic control, and was not linked to frequency of hypoglycemia and family history of diabetes. From the results above, we concluded that diabetic retinopathy in patients with pancreatic diabetes due to calcifying pancreatitis might be taken as evidence that such complications are primarily due to chronic hyperglycemia and the duration of diabetes mellitus rather than to genetic factors and other factors (body mass index, hypertension, serum total cholesterol and diabetic therapies).
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PMID:Diabetic retinopathy in Japanese patients with long-standing pancreatic diabetes due to calcifying pancreatitis. 786 4

Proteinuria and nephropathy have been found to cluster in families of non-insulin-dependent diabetic (NIDDM) Pima Indian, and in Caucasian insulin-dependent diabetic (IDDM) patients. No information is at present available for Caucasian NIDDM patients. The aim of the present study was to determine whether micro-macroalbuminuria (AER+) is associated with albumin excretion rate abnormalities in diabetic and non-diabetic siblings of probands with NIDDM and AER+. We identified 169 Caucasian families with one NIDDM proband (the patient with longest known NIDDM duration) (101 families with only NIDDM siblings, 33 families with both NIDDM and non-NIDDM siblings and 35 families with only non-NIDDM siblings). Of the probands 56 had AER+ [Prob-NIDDM-(AER+)], 78 had AER-[Prob-NIDDM-(AER-)], 74 siblings of Prob-NIDDM-(AER+), and 113 siblings of Prob-NIDDM-(AER-) also had NIDDM. Data on albuminuria and retinopathy from multiple sibling pairs when the size of the sibship was more than two was adjusted according to a weighting factor. The odds ratio for AER+, in siblings of Prob-NIDDM-(AER+) adjusted for age, hypertension, glycated haemoglobin A1c and other confounding variables was 3.94 (95% confidence intervals: 1.93-9.01) as compared to siblings of Prob-NIDDM-(AER-). The 74 siblings of Prob-NIDDM-(AER+) had higher prevalence of proliferative retinopathy than siblings of Prob-NIDDM-(AER-) (14 vs 2%; p < 0.01). We also identified 66 non-diabetic siblings of 41 NIDDM probands with AER+ and 36 non-diabetic siblings of 27 NIDDM probands with AER-. Albumin excretion was two times higher, although still within the normal range, in the non-diabetic siblings of Prob-NIDDM-(AER+) than in siblings of Prob-NIDDM-(AER-) [median = 13.5 (range 0.5-148) vs 6.6 (range 1-17) micrograms/min (p < 0.05)]. In conclusion higher rates of albumin excretion aggregate in Caucasian families with NIDDM. Proliferative retinopathy is more frequently observed in families showing a clustering of AER+ and NIDDM. These findings suggest that familial factors play a role in the pathogenesis of renal and retinal complications in NIDDM.
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PMID:Clustering of albumin excretion rate abnormalities in Caucasian patients with NIDDM. The Italian NIDDM Nephropathy Study Group. 924 3

Diabetic nephropathy clusters in families, suggesting an inherited predisposition. Parental history of hypertension and of Type 2 diabetes mellitus have been associated with nephropathy in offspring with Type 1 diabetes in some studies but not in others. The associations of parental history of hypertension and of diabetes with both albuminuria and proliferative retinopathy were studied in a large cross-sectional study of 3250 patients with Type 1 diabetes, from 16 European countries. Albuminuria was associated with hypertension in a parent (p < 0.01 in men, p < 0.05 in women), adjusted for age. Patients with a parental history of hypertension had a higher prevalence of hypertension (p < 0.001 in men, p < 0.01 in women) and a higher prevalence of parental diabetes (p < 0.001 in men, p < 0.001 in women). The association of albuminuria with parental hypertension was independent of parental diabetes in men but not women (OR = 1.28 in men p = 0.04, OR = 1.25 in women p = 0.09) and was not independent of hypertension in the patient him/herself in either sex. Albuminuria was associated with parental diabetes in women only (OR = 1.36, p = 0.04). This association was independent of both parental hypertension and hypertension in the patient herself. Proliferative retinopathy was not associated with parental hypertension or diabetes. The implications of these data are that both candidate genes for hypertension and Type 2 diabetes should be considered in the search for the genetic determinants of diabetic nephropathy.
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PMID:Parental history of hypertension and parental history of diabetes and microvascular complications in insulin-dependent diabetes mellitus: the EURODIAB IDDM Complications Study. 973 14


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