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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
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PMID:Hyperinsulinemia--how innocent a bystander? 829 79

On the whole, diabetic microangiopathy can be understood as the clinical renal-retinal syndrome. About 10% of all diabetics die of end-stage renal failure, more frequent in IDDM. With an incidence of 14% diabetic retinopathy is one of the major causes of blindness in adulthood. In the non-proliferative state, the pathological changes are limited to the retina, whereas the alterations affect both retina and vitreous in the proliferative state. Photocoagulation is the treatment of choice. If photocoagulatory treatment is not possible because of cataract, vitreous surgery (pars-plana vitrectomy) could improve visual prognosis. The clinical features hypertension, proteinuria and finally renal failure define the term "diabetic nephropathy". The increased intraglomerular pressure is the main pathological alteration of incipient nephropathy. Microalbuminuria essentially determines the prognosis: in IDDM it concerns the incidence of a manifest nephropathy, in NIDDM the excessively increased incidence of cardiovascular mortality. Sonographically, the kidneys are large with bright and wide parenchyma. Along with the development of end-stage renal disease the kidney size diminishes. According to Mogensen, nephropathy is divided into five stages: Stage 1, the early stage, is defined by hypertrophy and hyperfiltration. Stage 2 shows incipient structural changes without any clinical findings. Stage 3 is characterised by persistent microalbuminuria. Stage 4 leads to increasing renal failure and stage 5 to end-stage renal disease and the necessity of dialysis treatment. Incipient nephropathy demands a strict treatment of both hypertension and diabetes. In the meantime, ACE inhibitors are the treatment of choice. In case of dialysis treatment continuous ambulant peritoneal dialysis (CAPD) is usually preferred.
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PMID:[Diabetic microangiopathy]. 847 38

The author describes the assessment of the effectiveness of antihypertensive drugs according to the T-P (Trough-Peak) ratio, i.e. the effect at the end of the dosage period to the effect during its peak after subtraction of the placebo effect. He draws attention to methodological difficulties which make it so far difficult to compare data from the literature. It is, however, advisable in clinical practice of the treatment of hypertension to assess the blood pressure at the end of the dosage period rather than during the peak of effectiveness, as frequently practiced. Drugs with a long biological half-life are particularly useful. The most important criterion of effectiveness of antihypertensives is, however, their effect on the cardiovascular and cerebrovascular mortality and morbidity. Only on diuretics and beta-blockers extensive data are available indicating that they lead to a decline of the morbidity and mortality. Therefore they should be the drugs of first choice, in particular in elderly hypertonics. Data on calcium channel blockers, in particular nifedipine are controversial. ACE inhibitors are suitable in heart failure, asymptomatic dysfunction after acute myocardial infarction and in type 1 diabetes mellitus. Only at present investigations are under way to assess whether the effect of new and more expensive antihypertensives on mortality and morbidity is greater than the effect of diuretics and beta-blockers and whether they will be suitable drugs of first choice.
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PMID:[Evaluation of the effectiveness of antihypertensive therapy. Is the trough-peak ratio the determining factor?]. 868 81

Hypertension is both an exacerbating factor for, and a consequence of, diabetic renal disease. In diabetic patients, hypertension is associated with increased total body sodium secondary to impaired renal excretion, and increased vascular reactivity, notably to catecholamines and angiotensin II. The mechanisms causing these changes are discussed. Control of hypertension will slow the progression of diabetic renal disease and the inexorable decline in GFR. A number of studies now suggest that in proteinuric IDDM and NIDDM patients angiotensin converting enzyme inhibitors (ACE-I) may have additional reno-protective effects in addition to their hypotensive action. In addition ACE-I will reduce proteinuria and delay the onset of diabetic nephropathy in normotensive microalbuminuric IDDM and NIDDM patients. Use of ambulatory blood pressure monitoring indicates that such patients may not be truly 'normotensive'. On-going studies seem to suggest that the most reno-protective blood pressure is the lowest one achievable, as long as the patient remains asymptomatic. Further studies are required to assess the impact of blood pressure control, and especially ACE-I, on the incidence of end-stage renal failure. In addition, more direct comparisons between different pharmacological agents in early diabetic renal disease would be useful.
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PMID:The management of hypertension in diabetes: with special reference to diabetic kidney disease. 873 20

Microalbuminuria (MA) is a term used for urinary albumin excretion between 20 and 200 micrograms/min. or 30-300 mg/24 h. This definition is not used by all authors. In addition, various methods may influence the results. The significance of MA concerns the prognosis in diabetics. For the juvenile type 1 diabetes nephropathy is the most important complication. In adult type 2 diabetics the prognosis concerns mainly cardiovascular death. The excess mortality to be attributed to MA is several fold in type 1 diabetes, less in the adult onset type variety. MA is the expression of an incipient general disease of blood vessels touching as much the kidney as the heart. According to the presence or absence of other vascular damage. MA develops toward nephropathy or cardiovascular complications. The features leading to or worsening MA are elevated blood pressure, poor glucose control, elevated lipoproteins, diminished insulin sensitivity and probably smoking. Retinopathy is an indicator for particularly sensitive patients responding with the development of MA upon only mildly elevated blood pressure or poor metabolic control. The prevalence of MA is close to 20% for both types of diabetes. Non-diabetic persons under 60 years of age exhibit MA in 2-10%, the elderly in 20-30%. For non-diabetic persons with hypertension MA is reported to be present in 19%. Over a time span of 5 years, 19% of type 1 patients with MA develop proteinuria of more than 300 mg/24 hours. In a third of cases albumin excretion normalises. In the remaining half a small progression of MA occurs. For type 2 patients the increased mortality risk is restricted to the first 5 years, thereafter the survival curves return to those of patients without MA. In these patients the excess mortality is already present at albumin excretion rates above 10 micrograms/min. Higher values have, therefore, to be considered pathological. For the treatment of the syndrome ACE-inhibitors and ev. Ca-antagonists (with the exception of dihydropyridine, nifedipine) are recommended. They reduce albumin excretion by 50%. In a single study (yet) with type 1 diabetes mortality also was reduced by 40-50%. This would imply that the excess mortality could be halved in patients undergoing this treatment.
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PMID:[Microalbuminuria in diabetes mellitus--illness or symptom?]. 873 41

A total of 168 patients with non-insulin dependent diabetes (NIDDM) followed over 10 years were recruited in this study. The patients were divided into two groups: Group 1 patients had a stable renal function (N = 96) and Group 2 had a declining renal function (N = 72). Group 1 included those whose serum creatinine was normal five years ago but had increased to > or = 2 mg/dl or those who has reached end-stage renal failure (requiring dialysis) by the time of study. All patients were genotyped for the insertion/deletion (I/D) polymorphism of the ACE gene, the M235T polymorphism of the angiotensinogen (Atg) gene and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1) gene. The genotype frequency distributions of M235T Atg and the A116C AT1 gene polymorphisms were not different between Group 1 versus Group 2. While the frequency of the ACE DD genotype in Group 1 (7.3%) was comparable to that of the general population, the DD frequency was significantly higher in Group 2 (26.4%) than in Group 1 (odds ratio, 4.56; 95% confidence interval, 1.80 approximately 11.56, P < 0.001). Among all 168 patients studied, the renal survival rate was significantly lower among DD than ID (P < 0.005) or II patients (P < 0.001). In patients with a declining renal function (Group 2), those with the DD genotype had a significantly shorter time interval from onset of diabetes to the initiation of dialysis (13.4 +/- 1.4 years) than those with ID (20.7 +/- 1.2 years, P < 0.01) or II genotypes (17.5 +/- 1.1 year, P < 0.01). Analysis of the clinical course of the three ACE genotypes revealed that the majority (95%) of patients with the DD genotype who had albuminuria progressed to end-stage renal disease within 10 years of diagnosis of diabetes. Our analysis also revealed that initiation and continuation of dialysis are associated with a progressive decrease in the frequency of the DD genotype. These results indicate that, in NIDDM, the ACE DD genotype has a high prognostic value for progressive deterioration of renal function. Moreover, the DD genotype appears to increase the mortality once dialysis is initiated.
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PMID:Angiotensin I converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus. 884 Feb 99

Prospective registry of newly diagnosed cases of insulin-dependent diabetes mellitus in subjects under 20 years began in 1988 in Aquitaine, Lorraine, Basse- and Haute-Normandie (population base = 2,288,018 inhabitants under 20). The registry gave a complete coverage of the population as the capture-recapture method gave a 98% yield. The mean annual incidence was 7.6/100,000 for the period 1988-1990. A specific survey aimed at describing clinical and biological presentation at diagnosis. The main symptom was polyuria in 98% of the cases, fatigue in 58% and weight loss in 44%. Abdominal pain was reported in 34% of the cases. Diagnosis was ascertained by measurement of plasma glucose, which was > or = 11 mmol/l in 95% of the cases and associated with ketonuria in 84% of the children. Coma in 13% of the children and acidosis (total CO2 < or = 18 mmol/l) in 48% showed the severity at diagnosis. Ketonuria and acidosis were significantly more frequent in the younger age group (0-4 yr). Diagnosis was made by a general practitioner in the majority of the cases; conversely insulinotherapy was initiated at the hospital in 95% of the cases. Initial insulin treatment was 2 daily injections. Following the French experience the collaborative network EURODIAB ACE has undertaken the same survey among the European Registries. Important geographical variations in incidence rates of IDDM in children has been reported across Europe but it is not known whether this interferes with presentation at diagnosis of the disease.
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PMID:[Diagnosis of insulin-dependent diabetes in children: data from the incidence registry]. 893 70

Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) versus an ACE inhibitor (lisinopril) on albuminuria, arterial blood pressure, and glomerular filtration rate (GFR) in hypertensive IDDM patients with diabetic nephropathy. We performed a 1-year, double-blind, double-dummy, randomized, controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic nephropathy. Three patients dropped out, and results for the remaining 49 (25 nisoldipine, 24 lisinopril) are presented. Diuretics were required in 10 nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded every 6 months. Mean arterial blood pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril group versus an increase of 11% (-3 to 27) in the nisoldipine group (P = 0.001). Fractional albumin clearance was reduced 37% (95% CI 4-59%) in the lisinopril versus an increase of 35% (8-69%) in the nisoldipine group (P < 0.01). GFR decreased from 85 +/- 5 ml x min(-1) x 1.73 m(-2) to 73 +/- 5 in the lisinopril group and from 84 +/- 6 to 80 +/- 7 in the nisoldipine group (P < 0.05). The effect of study medication on albuminuria and GFR was independent of changes in systemic blood pressure and baseline variables in multiple regression analyses. In summary, lisinopril reduced albuminuria, but also GFR, to a greater extent than did nisoldipine in hypertensive IDDM patients with diabetic nephropathy during the 1st year of treatment. Longer follow-up is required to clarify whether these drugs have different renoprotective effects.
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PMID:Differences between nisoldipine and lisinopril on glomerular filtration rates and albuminuria in hypertensive IDDM patients with diabetic nephropathy during the first year of treatment. 903 6

Diabetic nephropathy affects a subset of about 40% patients with Insulin-Dependent Diabetes Mellitus (IDDM); it also develops in a less defined percentage (30-50%) of patients with non Insulin-Dependent Diabetes Mellitus (NIDDM), after a period of 15-20 years. It is usually divided in 5 stages: the first 3 are characterized by renal hypertrophy and increased glomerular filtration surface area (I stage) followed by glomerular histological lesions (II stage) and early nephropathy with microalbuminuria (III stage). At these stages nephropathy is still reversible by medical treatment (ACE inhibitors) and good metabolic control. Aim of this study was to assess the usefulness of duplex sonography with Doppler wave form analysis in the evaluation of early diabetic nephropathy, in order to detected patients at risk for irreversible renal disease. Fifteen patients (10 males and 5 females) aged 28-46 years, affected by IDDM were studied; 15 healthy subjects (7 males and 8 females) aged 20-45 years composed the control group. All of them underwent duplex Doppler sonography of kidney; a scanner with a 3.5 MHz transducer (Toshiba 270 SSA) was used. All patients had renal function tests within normal range. Pulsatily Index (P.I.) and Resistive Index (R.I. of Doppler waveform were obtained at the interlobar arteries; the average value of 3 bilateral measurements was taken. Doppler sonography was done by the same authors without knowledge of the patient group (case or control). Both indexes (P.I. and R.I.) resulted to have higher values in patients with IDDM compared to controls: P.I. = 1.46 +/- 0.30 vs. 1.07 +/- 0.06, p < 0.05; R.I. = 0.77 +/- 0.09 vs 0.60 +/- 0.03, p < 0.05. Even if our data have to be confirmed by further studies, they suggest that duplex Doppler sonography may be a useful complementary test in the evaluation of diabetic nephropathy, even in the early stages.
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PMID:[Pulsed-wave color Doppler echography of the intrarenal vessels in patients with insulin-dependent diabetes mellitus and incipient nephropathy]. 916 57

Diabetic nephropathy accounts for almost a third of all causes of ESRD. Microalbuminuria screening among diabetics can offer early detection of incipient nephropathy. Aggressive treatment with ACE inhibitors may delay the onset of overt renal failure or delay its progression. Furthermore, intensive control of blood glucose has also been proven to prevent the microvascular complications of diabetes and should be pursued in both IDDM and NIDDM. The high association of diabetes mellitus with hypertension presents another problem to the clinician. It is necessary to control blood pressure to prevent further progression of renal failure. The choice of antihypertensive medications, however, becomes a therapeutic dilemma because of the metabolic and lipid disturbances that some drugs can cause. ACE inhibitors, CCBs, alpha-agonists, and low-dose diuretics, alone or in combination, may be tried to normalize blood pressures. Although beta-blockers are widely used and effective in nondiabetics, these agents should be considered the drugs of last resort because of their adverse effects, which are particularly troublesome for diabetics. Moderate protein restriction should also be advocated as a helpful adjunct to therapy.
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PMID:Diabetic nephropathy. 916 51


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