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Query: UMLS:C0011849 (diabetes)
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According to international consensus, microalbuminuria is defined as an elevated urinary albumin excretion rate (UAER) of 20-200 micrograms/min, which is below the proteinuric range. Nephropathy is a major complication in IDDM, seen in about 30% of patients after many years of diabetes. Increasing microalbuminuria is an excellent marker of subsequent nephropathy in these patients. End-stage diabetic nephropathy is also important in NIDDM, but in most Western countries this serious complication eventually develops in only 5 to 10% of cases, whereas the majority of patients die before this from cardiovascular disease. In completely healthy individuals there is no clear correlation between age and UAER, at least up to about 70 years of age. The mean excretion rate is around 5 micrograms/min, with a considerable range, but excretion only rarely exceeds 15 micrograms/min. In population studies among middle-aged and elderly individuals, higher values are seen. In newly diagnosed NIDDM about 40% of patients show an excretion rate above 15-20 micrograms/min. There is a significant but not precise correlation between albumin excretion rate and glycemic control, and usually UAER is reduced by standard antidiabetic treatment. In a considerable number of patients, high values cannot be reduced. In the course of NIDDM about 20-30% of patients show microalbuminuria. In patients with known diabetes, microalbuminuria is related not only to subsequent diabetic proteinuria, but even more strongly to early death, mainly from cardiovascular disease. Even slight microalbuminuria (15-40 mg/l in early morning urines) is clearly associated with increased mortality. In subjects with newly detected elevated blood glucose (by screening) microalbuminuria also predicts early mortality. The mechanisms are not established, but several arteriosclerosis-related risk factors are seen more frequently in patients with microalbuminuria, e.g. lipid abnormalities, elevated systolic blood pressure (BP), hemostatic measures, as well other markers of cardiovascular disease. Usually there is a significant but not precise correlation between BP and UAER in groups of patients throughout the course of diabetes. New studies document that also in the elderly background population microalbuminuria is a significant risk factor for early death, maybe even stronger than the established risk markers, which thus may be confounded with the presence of microalbuminuria.
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PMID:Microalbuminuria in non-insulin-dependent diabetes. 129 5

Chronic microvascular complications are important causes of mortality and morbidity in people with diabetes mellitus. After 10 years of disease, nearly 70% of diabetics are affected by retinopathy and about 40% by nephropathy. Genetic factors have a great influence on the development of diabetic microvascular complications, as pointed out by their association with HLA system and Na/Li countertransport, but epidemiological and experimental studies show that the greater role is played by the metabolic milieu. Protein glycation, sorbitol pathway and lipid abnormalities can be responsible for early and fast development of the microvascular complications of diabetes mellitus.
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PMID:[Microvascular complications in diabetes mellitus. Pathogenetic aspects]. 129 46

The long-term complications of diabetes can have a devastating effect on an individual's self-esteem and outlook on life. Some preliminary studies have suggested that normalization of blood glucose levels may prevent or reverse the complications of diabetes in some individuals. Nutrition and diabetes meal planning play a critical role toward achieving this normalization. It is our job as diabetes educators to fully assess a patient's eating and life-style habits, as well as to recognize any complications from diabetes that the patient may be coping with at this time. Depending on the type of complication, diet alterations may need to be made to meet the patient's current needs, ie, reducing fiber content of the diet temporarily in patients with mild gastroparesis, or increasing the protein content of the diet in patients with nephropathy and a foot ulcer. By setting positive, attainable goals, the individual with diabetes may lead a healthier, more productive life in which the complications from diabetes can be prevented, reduced, or better tolerated.
Diabetes Educ
PMID:Nutritional considerations for other complications of diabetes. 129 3

We prospectively conducted a hospital based study to determine the prevalence of vascular complications in NIDDM and their risk factors. Using standard protocol for interviewing, physical examination and laboratory investigations, we studied 207 patients from the diabetic clinic and medical outpatient department (ratio 3.9:1) by systematic sampling. The prevalence of hypertension, coronary heart disease cerebrovascular disease, peripheral and large vessel disease was 22.2, 22.2, 8.2, 21.3 and 34.8 per cent respectively. We found that the prevalence of small vessel disease, retinopathy and nephropathy was 34.3, 25.1 and 12.5 per cent respectively. The complications were slightly higher in females and increased with duration of diabetes. By univariate and logistic regression analysis, we found that the risk factors of large vessel disease were body mass index, diastolic blood pressure, duration of diabetes and for small vessel disease were duration of diabetes and high uric acid.
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PMID:Vascular complications in noninsulin dependent diabetes mellitus (NIDDM) in Srinagarind Hospital, Khon Kaen. 130 93

1. It has been proposed that raised erythrocyte sodium-lithium countertransport activity in type 1 diabetic patients is associated with an increased risk of developing diabetic nephropathy. Diabetic patients with established nephropathy would therefore be expected to have high activity. 2. Standard sodium-lithium countertransport activity, sodium affinity (Km) and maximum velocity (Vmax) were measured in type 1 diabetic patients at different stages of diabetic nephropathy and in appropriately matched uncomplicated diabetic patients and normal control subjects. 3. A small proportion (15%) of patients with nephropathy had standard sodium-lithium countertransport activity higher than the control range. However, mean standard sodium-lithium countertransport activity in the diabetic patients with nephropathy [mean +/- SEM, 0.26 +/- 0.12 mmol of Li+ h-1 (l of cells)-1] was not significantly higher than in the uncomplicated diabetic patients [0.27 +/- 0.03 mmol of Li+ h-1 (l of cells)-1] or in the normal control subjects [0.25 +/- 0.02 mmol of Li+ h-1 (l of cells)-1]. 4. There were marked changes in the kinetic characteristics of the sodium-lithium countertransport in the diabetic patients with nephropathy so that there were decreases in both Km and Vmax. 5. These kinetic changes could not be attributed to an effect of either renal failure per se or the duration of diabetes. 6. The characteristic kinetic changes in sodium-lithium countertransport may indicate underlying alterations in membrane function with the onset of nephropathy in type 1 diabetes.
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PMID:Changes in erythrocyte sodium-lithium countertransport kinetics in diabetic nephropathy. 131 15

Renal disease is one of the most common and severe complications of diabetes mellitus. The hallmark of the disease, glomerulosclerosis, is characterized by an accumulation of extracellular matrix in the mesangial areas, leading to progressive obliteration of the vascular spaces. The role of the metabolic derangements of diabetes mellitus in the development of these lesions is incompletely understood. One of the consequences of hyperglycemia is the formation of advanced glycosylation end products (AGEs), which result from a series of rearrangements secondary to nonenzymatic reaction of glucose with proteins. Specific receptors for proteins modified by AGEs, present in several cell types, were recently described in human and rat mesangial cells. Furthermore, exposure of mesangial cells to AGEs was followed by an increase in fibronectin production. In the present study we show evidence that mouse mesangial cells exhibit an increase in collagen type IV mRNA and peptide synthesis after exposure to AGEs. Antibodies to AGE receptors prevent this increase, indicating that the response is AGE-receptor-mediated. In addition, anti-platelet-derived growth factor abrogates the AGE response, suggesting that platelet-derived growth factor acts as an intermediate factor. Transcription assay reveals that the elevated mRNA levels are due to an increase in the transcription rate, rather than to an increase in the stability of the message. Finally, the mRNAs coding for laminin and heparan sulfate proteoglycan are also increased after exposure to AGE, whereas glyceraldehyde 3-phosphate dehydrogenase mRNA levels remain constant. The increase in extracellular matrix mRNAs seen in the current study suggests that AGE formation in vivo may be one of the metabolic events leading to the development of diabetic glomerulosclerosis.
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PMID:Receptor-specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet-derived growth factor. 131 71

In order to assess the potential role of the plasma membrane sodium-proton (Na+/H+) exchanger in the pathogenesis of diabetic nephropathy, we investigated 32 insulin dependent (type 1) diabetic patients and 21 control subjects. We tested the Na+/H+ exchange as the rate of amiloride sensitive and sodium dependent volume gain of platelets suspended in sodium propionate. Patients with diabetic nephropathy had significantly increased rates of Na+/H+ exchange (0.31 +/- 0.06 s-1 x 10(-2)) when compared to those without nephropathy (0.24 +/- 0.07, p less than 0.05) or to a control group (0.23 +/- 05, p less than 0.05). Nine patients who were classified as hypertensive had a highly significant increase in the Na+/H+ exchange rates when compared to 23 non-hypertensive diabetic patients: 0.33 +/- 0.04 versus 0.24 +/- 0.06 (p less than 0.001). There was no significant correlation between the Na+/H+ exchange rates and age, diabetes duration, glycated hemoglobin or fructosamine levels on the day of the test. In summary, the data presented here demonstrate an increase in the Na+/H+ exchange rate in insulin-dependent diabetic patients with nephropathy and hypertension.
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PMID:Increased platelet sodium-proton exchange rates in insulin-dependent (type 1) diabetic patients with nephropathy and hypertension. 132 Jul 32

IDDM patients with incipient and overt nephropathy have been found to exhibit an overactivity of RBC sodium-lithium countertransport. To explore the physiological relevance of this finding, we measured the activity of Na+/H+ antiport in serially passaged cultured skin fibroblasts from IDDM patients with and without nephropathy and from normal, nondiabetic control subjects. Na+/H+ antiport activity (measured as the rate of amiloride-sensitive Na+ influx at pHi = 6.4, extracellular pH = 8.0, and [Na+] = 1 mM) was elevated significantly in IDDM patients with nephropathy compared with IDDM patients without nephropathy and nondiabetic control subjects (13.35 +/- 3.8 vs. 8.54 +/- 2.0 vs. 7.33 +/- 2.3 nmol Na+.mg protein-1.min-1; P less than 0.006 and P less than 0.001, respectively). A kinetic analysis of Na+/H+ antiport activity showed that the raised activity in IDDM patients with nephropathy was caused by an increased Vmax for extracellular Na+. Km values were similar in the three groups. pH-stimulated amiloride-sensitive Na+ influx also was higher under baseline conditions and after serum stimulation in cells from IDDM patients with nephropathy. pHi values were significantly higher, both during active proliferation and after 10-min exposure to serum, in cells from IDDM patients with nephropathy, compared with IDDM patients without nephropathy and nondiabetic control subjects. Serum-stimulated incorporation of [3H]thymidine into DNA was greater in IDDM patients with nephropathy than in the other two groups (35.7 +/- 18.9- vs. 17.4 +/- 7.5- vs. 11.9 +/- 8.7-fold stimulation above baseline; P less than 0.01 for both.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Oct
PMID:Na+/H+ antiport activity and cell growth in cultured skin fibroblasts of IDDM patients with nephropathy. 132 25

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-ACE (r = 0.98, P less than 0.001) and between retinopathy and S-ACE levels (r = 64, P less than 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.
Diabetes Res Clin Pract 1992 Jun
PMID:Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus. 133 Apr 63

Hyperglycemia is an important risk factor for the development of retinopathy and nephropathy in people with diabetes mellitus. There are few population-based data on changes in glycemia over time. The purpose of this study was to examine changes in glycemia, as measured by glycosylated hemoglobin in 1980 to 1982 and in 1984 to 1986, in a large population-based study of people who were diagnosed to have diabetes before the age of 30 years and who used insulin (n = 697). Glycosylated hemoglobin was measured by a microcolumn technique at both examinations. There was a significant (P < .001) fall in the mean glycosylated hemoglobin from 10.8 to 10.1% over the 4-year interval of the study. In contrast, there was no change in the glycosylated hemoglobin (6.2%) in a similarly aged nondiabetic comparison group over the same period. The decrease in mean glycosylated hemoglobin over the 4-year period in the diabetic group was associated with several characteristics of diabetes management. These include changes in the insulin regimen (going from intermediate- or long-acting insulin only to combinations with short-acting insulin), an increase in the number of doses of insulin per day, and a higher frequency of self-monitoring of blood glucose level. It was also associated with an increased number of reported insulin reactions. These data suggest that recent changes in treatment and management of diabetes may be related to a significant decrease in glycemia.
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PMID:Change in glycemia in a four-year interval in younger-onset insulin-dependent diabetes. 134 79


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