IDDM Complications Research Articles

日系米人非糖尿病者における虚血性心疾患発症予知因子としての尿中微量アルブミンの臨床的意義

Urinary microalbumin (UMA) is recognized as a marker of renal complications in IDDM and is associated with increased mortality in NIDDM. We investigated the association of UMA with cardiovascular risk factors in 380 non-diabetic Japanese-Americans. Among 380 of these subjects, 24 (6.3%) were found to have elevated UMA (30-260μg/ml) at the baseline. The subjects with elevated UMA had significantly higher systolic and diastolic blood pressure (BP), triglycerides (TG) and total cholesterol (CH) than those without UMA. Among 355 normoalbuminuric subjects, a 3-year follow-up study indicated that 316 remained at normal levels (NN group) while 39 (11.0%, NM group) developed UMA or proteinuria (260μg/ml∼). Compared to normoalbuminuric subjects, subjects who developed UMA or proteinuria had significantly higher levels of systolic BP, TG, serum glucose, total immunoreactive insulin (ΣIRI) levels during 75g OGTT, and ischemic ECG abnormalities but lower HDL-CH levels at baseline. Only 4.2% of the subjects without hypertriglyceridemia, hyperinsulinemia, high BP and glucose intolerance developed UMA during the 3-year follow-up period. The incidence of UMA was found to increase in accordance with the number of these factors present, reaching 50% in subjects having all four factors.To confirm whether UMA is a new potent marker of cardiovascular risk, we investigated the clinical data of these 355 normoalbuminuric subjects for a 6-year period preceding the baseline. The subjects who developed UMA were found to have higher serum glucose, BP, TG and insulin levels but lower HDL-CH levels than those who remained normoalbuminuric, even in the 6-year period before the baseline.UMA, which is associated with hypertriglyceridemia, hyperinsulinemia, high BP and glucose intolerance, may thus be a potent marker of increased cardiovascular risk in non-diabetic Japanese-Americans.

Eating disorders and IDDM. A problematic association.

IDDM and eating disorders are common conditions in young women. Whether a specific association exists between these two disorders remains controversial. Some studies have suggested an increased incidence of eating disorders in young women with IDDM, whereas others have not detected such an increase. These differences may be attributable, at least in part, to methodological issues in study design, measurement tools, and relatively small sample sizes. Whether the prevalence of eating disorders in IDDM is increased will be resolved only by larger studies that use standardized diagnostic interviews. We suspect that certain aspects of IDDM and its management may trigger the expression of an eating disorder in susceptible individuals. Required dietary restraint and weight gain related to diabetes management are the factors most likely to be implicated. Eating disorders are relatively common in young women with IDDM and may contribute to impaired metabolic control with hypoglycemia and DKA, and to long-term microvascular complications of diabetes. Omission or reduction of required insulin, an extremely common means of weight control in these young women, is likely an important factor in this regard. Further research is required to determine more precisely the relationship between IDDM and eating disorders, and the effects of eating disorders on metabolic control and chronic complications of IDDM.

Diabetes mellitus and macrovascular complications. An epidemiological perspective.

It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.

The association of waist-hip ratio and risk factors for development of IDDM complications in an IDDM adult population

The role of waist-to-hip ratio (WHR) in the metabolic disturbance of IDDM has not been widely explored. Cross-sectional data from the Epidemiology of Diabetes Complications Study were used to examine the associations between WHR and risk factors for IDDM complications such as lipid or lipoprotein levels, blood pressure and fibrinogen. A total of 586 adults (≥ 18 years of age) were examined. WHR was calculated as the mean of duplicate waist circumference measurements made at mid-point between the iliac crest and the lower costal margin in mid-axillary line divided by the mean of duplicate maximum hip measures. WHR was positively correlated with total cholesterol, LDL-cholesterol, triglycerides, systolic and diastolic blood pressure and fibrinogen univariately for both sexes. WHR was negatively correlated with HDL-cholesterol. These correlations remained significant after adjustment for age among females and became less strong, although still significant, for males. The independent effects of WHR to these IDDM risk factors, assessed by multiple linear regression, indicated WHR was related to adverse lipid and lipoprotein levels, but not to fibrinogen or blood pressure. These findings underscore the importance of targeting intervention to IDDM individuals who have a high WHR to reduce known risk factors for IDDM complications especially those for cardiovascular disease, and is consistent with the hypothesis that insulin resistance may have a role to play in IDDM complications.

Effect of Long-term Treatment with Continuous Subcutaneous Insulin Infusion (CSII) on Progression of Diabetic Complications in IDDM

Effect of Long-term Treatment with Continuous Subcutaneous Insulin Infusion (CSII) on Progression of Diabetic Complications in IDDM

Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II

Prevalence of complications in IDDM by sex and duration. Pittsburgh Epidemiology of Diabetes Complications Study II

Early Onset of Increased Transcapillary Albumin Escape in Awake Diabetic Rats

Alteration in transcapillary albumin escape rate (TERalb) is an indicator of changes in macromolecular movement at the capillary filtering bed, which can change the balance of Starling forces for fluid movement from the vasculature to the interstitium and has an impact on volume homeostasis. TERalb can be affected by morphological changes in the capillary membrane and/or alterations in the Starling forces driving larger solutes across the capillary membrane via convection. Previous studies have demonstrated an increased TERalb in established insulin-dependent diabetes (IDDM); however, whether increased TERalb is the result of morphological alterations in the microvasculature or contributes to microangiopathies could not be resolved. TERalb was examined in awake Wistar rats with untreated IDDM induced by streptozocin infusion (65 mg/kg body wt i.v.) at 24 h and 7 and 15 days and compared with control and insulin-treated 7-day IDDM rats. Increased TERalb occurred at the 24-h time point and remained elevated at 7 and 15 days of IDDM (P less than 0.05). Blood volume remained unchanged; however, systemic protein concentration increased from 4.9 +/- 0.1 g/dl in controls to 6.4 +/- 0.4 g/dl in 15-day IDDM rats. Blood glucose was significantly increased, and glycosuria was evident at all three time points of IDDM. The observed increase in TERalb within 24 h of IDDM is indicative of a functional change in the Starling forces in the capillaries, because specific morphological capillary damage is not evident at this time point in the model. The early onset of TERalb in IDDM could indicate functional changes, such as capillary hypertension, and may contribute to future vascular complications in established IDDM.

HDL metabolism in diabetes.

Based on the data reviewed, it is necessary to conclude that diabetes is associated with profound changes in HDL metabolism. However, once we go beyond this simple generalization, it is apparent that the relationship between diabetes and HDL metabolism is not a simple one. A good deal of the complication evolves from the fact that IDDM and NIDDM seem to affect HDL metabolism quite differently, with the only apparent similarity the fact that plasma HDL-cholesterol concentration can be low in untreated patients with either IDDM or NIDDM. Thus, in patients with IDDM the primary event seems to be related to the insulin-deficient state, which results in a decrease in HDL turnover rate and resultant decline in plasma HDL-cholesterol concentration. In contrast, HDL turnover appears to be accelerated, not reduced in patients with NIDDM, and the low plasma HDL-cholesterol concentration is a consequence of the increased turnover rate. In addition, patients with NIDDM are not absolutely insulin deficient, and available evidence suggests that the higher the plasma insulin level, the lower the plasma HDL-cholesterol concentration in these patients. The differences noted above in the effect of IDDM and NIDDM on HDL metabolism are of great interest, and, unfortunately, not very well understood. There is, however, one additional difference, which may be of paramount clinical importance. For reasons not totally clear, plasma HDL-cholesterol concentrations in patients with IDDM treated with insulin are not lower than normal, and even tend to be higher than these values in a nondiabetic population. Possibly as a result of this phenomenon, there is no evidence that changes in plasma HDL-cholesterol concentration play a role in the development of macrovascular complications in IDDM. Although it is apparent from the considerations discussed in this review that a great deal more needs to be learned about the effect of insulin deficiency on HDL metabolism, changes in HDL metabolism do not appear to be clinically important in patients with IDDM. Unfortunately, this does not appear to be the situation in patients with NIDDM. Plasma HDL-cholesterol concentrations are lower than normal in patients with NIDDM, and this finding seems to be related to increased morbidity and mortality from CAD. Furthermore, there is no form of anti-diabetic treatment, irrespective of how effective it has been in achieving glycemic control, that has been shown to substantially increase plasma HDL-cholesterol level. Indeed, it has been difficult to demonstrate a consistent effect of any therapeutic approach on plasma HDL-cholesterol concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

1231 IDIOPATHIC HYPERCALCIURIA (IH): A POTENTIAL CAUSE OF RENAL DISEASE IN CHILDREN WITH INSULIN DEPENDENT DIABETES MELLITUS (IDDM)

Renal disease is a common complication of IDDM. The pathogenesis is believed to be microvascular and to increase with duration of IDDM. Hypercalciuria causes renal dysfunction and has been reported in children with IDDM. A group of children (157) with IDDM had urine and blood collected after a 10 hour fast. Thirty-seven age similar non-diabetic (ND) subjects were controls. Urine calcium (Ca), phosphate (PO4) and creatinine (Cr) were measured. The Ca/Cr and PO4/Cr ratios were calculated as an indicator of urinary excretion. IH (definition: Ca/Cr 2 SD>mean for ND) was found in 45 (29%) of the IDDM subjects (6% prevalence in ND children). PO4/Cr in IDDM (1.2±0.06) was greater than ND (0.72±0.08) p<0.002. Ca/Cr correlated with PO4/Cr in subjects with IDDM while no relationship was found in ND. Ca/Cr correlated both with coincident serum glucose (r=0.34, p<0.001) and glycosylated hemoglobin (r=0.25 p<0.001) but was not related to duration of diabetes or the current insulin dose. Both Ca/Cr and PO4/Cr correlated inversely with serum PO4 in IDDM; serum PO4 correlated directly with PO4/Cr but was not related to Ca/Cr in ND. PTH levels in ND and IDDM children were normal. Conclusion:1) a defect in tubular reabsorption of Ca and P exists in IDDM that is related to blood glucose concentration; 2) the ion product of Ca3(PO4)2 in the urine of (29%) IDDM children exceeds the solubility constant and is 3 times that of the ND children; 3) IH may be a cause, previously unrecognized, of some renal complications of IDDM.

Effect of Treatment on the Long Term Complications of Iddm

Effect of Treatment on the Long Term Complications of Iddm