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Query: UMLS:C0011849 (diabetes)
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Diabetic renal disease is a clinical syndrome in which proteinuria is followed by the development of renal failure, and is commonly associated with the concomitant development of hypertension. In insulin-dependent diabetic (IDDM) patients, hypertension often first appears in the microalbuminuric phase of diabetic nephropathy whereas in non-insulin-dependent diabetic (NIDDM) patients, hypertension often antecedes nephropathy and may precede the diagnosis of diabetes. Antihypertensive regimens including diuretics, vasodilators such as hydralazine, beta-blockers and ACE inhibitors reduce proteinuria and delay the decline in renal function in IDDM patients with established nephropathy. No such data are as yet available for calcium antagonists. In microalbuminuric diabetic patients with hypertension, conventional antihypertensive agents, ACE inhibitors and calcium antagonists have been shown to decrease urinary albumin excretion. In the diabetic patient with normal blood pressure and microalbuminuria, there is much less information. It appears likely that ACE inhibitors reduce or retard the rate of increase in albuminuria in these patients. The effect on ultimately delaying or preventing renal failure remains unknown although the preliminary evidence is encouraging. Data on calcium antagonists remain inconclusive with some reports suggesting an increase in proteinuria with the dihydropyridine calcium antagonists. However, a recent longer term study suggested that nifedipine may prevent the rise in albuminuria which is generally observed in the untreated normotensive microalbuminuric subject.
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PMID:The management of diabetic proteinuria. Which antihypertensive agent? 150 44

OBJECTIVE--To determine whether there is an association between smoking and the self-reported morbidity of people with IDDM and to evaluate the nature of a possible interaction between smoking and IDDM in increasing the risk of morbidity among smokers with IDDM. RESEARCH DESIGN AND METHODS--Subjects were non-Hispanic whites aged 18-28 yr who participated in the Colorado IDDM Registry Follow-up Survey (case subjects, n = 24) or the 1985 NHIS (control subjects, n = 5876). Assessments of self-reported morbidity included any hospitalization in the past year; bed days, sick days, and limited-activity days in the past 2 wk; and ratings of poor health. The criteria outlined by Saracci were used to determine whether smoking was associated with greater morbidity among IDDM case compared to control subjects (smoking by IDDM interaction). RESULTS--Age- and sex-adjusted ORs, estimated from logistic regression, showed that people with IDDM reported excess morbidity compared with control subjects, regardless of smoking status. Smokers with IDDM reported morbidity 3-10 times as often as nonsmoking control subjects and were 2-3 times more likely to report morbidity than nonsmokers with IDDM. The smoking by IDDM interaction was more than multiplicative for all morbidity measures. Fifty to 75% of excess morbidity in young smokers with IDDM over simple additive effects was related to the interaction between smoking and IDDM. CONCLUSIONS--There was excess reported morbidity among people with IDDM who smoked, greater than that expected from the combined effects of smoking and IDDM. Smoking cessation in young people with IDDM may alleviate some of this excess, but more study is needed to determine whether smoking serves as an indicator of poor IDDM care practices or has a physiological impact that compounds the morbidity experienced by people with IDDM.
Diabetes Care 1992 Aug
PMID:Smokers with IDDM experience excess morbidity. The Colorado IDDM Registry. 150 27

Longitudinal studies have shown a large excess of cardiovascular mortality in insulin-dependent diabetic patients (IDDM) as compared to non-diabetic controls. Although diabetes appears to be an independent cardiovascular risk factor, increases in total and LDL-cholesterol together with a decrease of HDL-cholesterol are more pronounced in diabetics with cardiovascular disease. The general opinion, however, derived from a large number of cross-sectional studies, is that in well-controlled IDDM lipoprotein abnormalities are modest and only slightly different from matched non-diabetic controls. Most of the studies, however, used absolute criteria based on consensus statements and do not take the internal relations of the lipoproteins into account. When atherogenic indices (such as the relationship between total cholesterol and HDL-cholesterol or the Apo A1/apo B quotient) are used, 20 to 30% of an IDDM population considered to be in clinically acceptable control have to be considered pathological. This observation is even more important since the recent Diabetes Control and Complications Trial has shown that, especially in the younger group of patients, significantly higher total cholesterol and triglycerides and lower HDL-cholesterol were observed. Especially in these patients can diet and drug intervention be the most useful in the prevention of cardiovascular disease. These data are consistent with the fact that more sophisticated techniques have previously shown atherogenic changes in the composition of the VLDL-particles and lipoprotein enrichment in apo B. Since these techniques are not easily available in the clinic one has to refer to more classical techniques and the use of above mentioned atherogenic profiles to decide treatment.
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PMID:Atherogenic profiles in insulin-dependent diabetic patients and their treatment. 150 49

The aim of this study was to compare the effect of nasally administered glucagon in doses of 1 (A) and 2 mg (B), with 1 mg glucagon administered intramuscularly (C) in 12 C-peptide-negative IDDM patients. Spontaneous recovery (D) from insulin-induced hypoglycaemia in the same patients was used as reference. The mean age was 31.1 (21-48) years, diabetes duration 10.8 (2.7-31) years and HbA1c 7.7 (6.5-9.8)%. Hypoglycaemia was induced by i.v. insulin infusion. When blood glucose (BG) reached about 2 mmol/l either glucagon was administered or the patients recovered spontaneously. BG nadir was 1.6 (1.1-2.3) mmol/l. BG increments during the first 15 min after glucagon administration were: (A) 1.9 +/- 0.7 (0.4-3.0); (B) 2.5 +/- 0.7 (1.5-3.5); (C) 2.5 +/- 1.0 (1.2-4.7); and (D) 0.3 +/- 0.4 (0-1.0) mmol/l, respectively. All treatments were more effective, measured as increments in BG, than spontaneous recovery, P less than 0.00001. There was no difference between nasal treatment with 2 mg (B) and i.m. treatment (C), both being more effective than 1 mg (A) nasal treatment, P less than 0.1. BG continued to increase up to 10 mmol/l 90 min after i.m. glucagon administration, whereas it stabilized at a level of 4.6-6 mmol/l, 30-45 min after nasal administration. Eighty percent of the patients had side-effects to nasal administration - local irritation, rhinitis or sneezing. Half of the patients sneezed, without correlation with the delivered dose of glucagon. None of the patients had side-effects which would preclude further treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res Clin Pract 1992 Jul
PMID:Nasal glucagon in the treatment of hypoglycaemia in type 1 (insulin-dependent) diabetic patients. 151 60

Less than a quarter of the patients with juvenile-onset IDDM develop diabetic nephropathy during the first 20 years of diabetes. To study the determinants of this complication, we selected patients who had come with newly diagnosed IDDM to the Joslin Clinic between 1967 to 1972, and we examined them in 1986 to 1988, that is, 15 to 21 years after onset of diabetes. Using a case control design we compared three groups of cases, that is, advanced nephropathy (N = 43), only microalbuminuria (N = 41), and hypertension alone (N = 17), with a group of controls who remained normoalbuminuric and normotensive despite the long duration of IDDM (N = 61). In comparison with controls, patients with advanced nephropathy had more parents with hypertension (odds ratio 3.8), higher Vmax values of Na/Li countertransport in red blood cells (odds ratio 10.0 for the highest tertile), and higher mean arterial pressure during adolescence and early adulthood (odds ratio 3.1 for those above the median). They also had significantly poorer glycemic control during their first 12 years of diabetes. Patients with hypertension alone were similar to those with advanced nephropathy with regard to markers of predisposition to hypertension but differed from them with regard to glycemic control, having the best glycemic control of all the study groups. Patients who developed only microalbuminuria during 15 to 21 years of IDDM (some of whom will progress to overt proteinuria later) did not differ significantly from controls with regard to predisposition to hypertension. In conclusion, predisposition to hypertension is a major risk factor for the development of advanced diabetic nephropathy and essential hypertension during the first 20 years of IDDM.
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PMID:Predisposition to hypertension: risk factor for nephropathy and hypertension in IDDM. 151 93

Although hypertension is an important complication of diabetes it is unclear whether its association with other diabetic complications represents cause or consequence. Our study is a cross sectional evaluation of the relationship of blood pressure to renal structural and functional parameters. In 139 patients with insulin dependent diabetes for 18.9 +/- 7.4 years (mean +/- SD), we divided the patients into those with markedly increased mesangial volume fraction [Vv(mes/glom) greater than or equal to 0.37] and those with less [Vv(mes/glom) less than 0.37]. Hypertension (systolic BP greater than or equal to 160 and/or diastolic BP greater than 90 mm Hg or receiving BP medications) occurred in 29/40 with Vv(mes/glom) greater than or equal to 0.37. All 40 had clinical nephropathy with urinary albumin excretion (UAE) greater than 200 mg/24 hr. By two-way ANOVA creatinine clearance was lower and albuminuria was increased with both hypertension and the expanded mesangium. Also other measures of renal structure including filtration surface, index of interstitial fibrosis and index of arteriolar hyalinosis were increased by hypertension and mesangial expansion. Most patients with hypertension had other criteria for clinical nephropathy. Since, in these studies, we could not determine if hypertension contributed to or resulted from the renal lesions, we developed an estimate of the rate of mesangial expansion. We found that patients with normal BP (119 +/- 11/78 +/- 7 mm Hg) can be rapidly developing mesangial expansion. These studies support the view that the development of serious renal lesions can be independent of hypertension in IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship of systemic blood pressure to nephropathology in insulin-dependent diabetes mellitus. 151 95

A review of the putative risk factors associated with the development of coronary heart disease in diabetes is presented. Emphasis is given to the effect of nephropathy (persistent proteinuria) and hypertension on cardiovascular mortality in IDDM. Risk factors associated with CHD in NIDDM are also reviewed. Finally, possible reasons to explain the increased incidence of CHD associated with proteinuria in IDDM patients, including lipoprotein abnormalities, increased fibrinogen levels, increased platelet adhesiveness, and altered hemostatic variables, are discussed.
Diabetes 1992 Oct
PMID:Risk factors for coronary heart disease in diabetes mellitus. 152 26

Abnormal lipoprotein metabolism contributes to the increased risk of premature atherosclerosis in people with insulin-dependent (type I) diabetes. Although hypertriglyceridemia is common in those with untreated IDDM, treatment with conventional insulin therapy usually restores fasting lipoprotein profiles to nondiabetic levels. Intensive insulin therapy improves glycemic control and lipoprotein concentrations, but does not ameliorate the changes in lipoprotein composition described in people with IDDM. Some of these persistent changes in lipoprotein composition have been attributed to peripheral hyperinsulinemia associated with s.c. insulin therapy. The recent availability of implantable insulin-infusion pumps for treatment of IDDM has allowed the study of the effect of i.p. insulin delivery on lipoprotein metabolism. i.p. insulin therapy is capable of maintaining near normal plasma glucose levels while reducing the peripheral hyperinsulinemia. Although results have been contradictory, studies of i.p. insulin therapy may eventually help to determine whether some of the observed changes in lipoprotein metabolism and composition in people with IDDM are due to the peripheral hyperinsulinemia associated with s.c. insulin therapy.
Diabetes 1992 Oct
PMID:Plasma lipid and lipoprotein disorders in IDDM. 152 27

Normolipidemic patients of both sexes with insulin-dependent diabetes mellitus have the same pervasive changes in lipoprotein surface and core lipid composition. The disproportionate increase observed in their lipoprotein free (unesterified) cholesterol relative to the predominant surface phospholipid lecithin (phosphatidylcholine) is reflected by elevation of the FC-L ratio in their whole plasma, VLDL, HDL2, and HDL3. As a possible consequence of this qualitative disturbance, cholesteryl ester transfer is pathologically increased and the mass of cholesteryl ester transferred from HDL to VLDL + LDL is significantly greater in IDDM patients than in control subjects at 1, 2, and 4 hr (P less than 0.001). Consistent with accelerated CET in vivo, the TG-CE core lipid ratio was decreased in VLDL from six subjects (IDDM 9.5 +/- 0.8 vs. control 12.9 +/- 3.4; P less than 0.01) and increased in their HDL (diabetic 0.55 +/- 0.11 vs. control 0.42 +/- 0.04: P less than 0.025). These abnormalities in lipoprotein composition and CET do not correlate with glycemic control and persist after intensive management with s.c. insulin. They may be related to the peripheral hyperinsulinemia that is an unavoidable consequence of conventional s.c. insulin administration because preliminary studies indicate that these disturbances in lipoprotein composition and function are reversed when systemic insulin levels are lowered and insulin is delivered into the portal circulation from an i.p. catheter connected to an implanted programmable s.c. insulin pump.
Diabetes 1992 Oct
PMID:Effects of insulin treatment on lipoprotein composition and function in patients with IDDM. 152 28

In people with diabetes, the concentration of an individual lipoprotein or apolipoprotein can be highly variable and is totally different in the two major forms of the disease. Alterations in the concentrations of major lipids and lipoproteins are well characterized in both IDDM and NIDDM. In general, the lipoprotein pattern is antiatherogenic in individuals with IDDM who are treated and have optimal glycemic control. In contrast, NIDDM is associated with atherogenic changes of serum lipids and lipoproteins regardless of the mode of treatment. In people with both types of diabetes, the distribution of apoE phenotype seems to be similar to that in nondiabetic populations. IDDM patients with microalbuminuria show atherogenic changes of lipoproteins and have elevated levels of Lp(a), which is a risk factor of coronary artery disease. Whether glycemic control influences the concentration of Lp(a) is still an open question. An important issue is that the concentration of a lipoprotein can be normal without excluding compositional abnormalities that are potentially atherogenic. Such alterations are present in people with both IDDM and NIDDM. Consequently, it has been questioned whether the target values to start treatment should be lower in diabetic than in nondiabetic populations.
Diabetes 1992 Oct
PMID:Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus. 152 30


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