Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a slow start, beta-blockers have become widely used as first-line agents in the treatment of hypertension, and recommended as such in recently published guidelines. There is evidence that the beta1-selective agents are more efficacious than non-selective blockers that inhibit both beta1 and beta2 receptors. Notwithstanding some earlier evidence to the contrary, it appears that beta1-selective drugs are equi-effective in young and elderly whites, younger, ie, under mid 60s, blacks. It is with the combination of age and being black that beta-blockers are usually less useful than some other groups of antihypertensive drugs, most notably calcium antagonists and diuretics. Primary prevention studies indicate beta-blockers reduce the incidence of cerebro-vascular disease and coronary heart disease in younger patients but they appear less effective than diuretics in the elderly. Beta-blockers are particularly indicated in patients who have experienced a myocardial infarction where they are often under used. There is some evidence that even in post-infarction patients with co-existent chronic obstructive airways disease, usually regarded as a contra-indication, experience an improved 2-year survival with the use of beta-blockers. Recently they have also been demonstrated to improve prognosis in heart failure patients, previously regarded as a contra-indication. Likewise, recent studies have shown that atenolol was at least as effective as captopril in improving the outlook in hypertensive patients with non-insulin dependent diabetes. While earlier comparisons with the non-selective lipid soluble propranolol indicated otherwise, comparisons with beta1-selective agents have indicated a similar effect on quality of life assessments with angiotensin-converting enzyme inhibitors.
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PMID:New approaches to the uses of beta blocking drugs in hypertension. 1085 83

We studied the relationship of coronary artery calcification (CAC), a marker of coronary atherosclerosis, with prevalent clinical coronary artery disease (CAD) and established cardiovascular disease (CVD) risk factors in a type 1 diabetic population. At the 10-year follow-up examination of the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study cohort, 302 adults (mean age 38.1 +/- 7.8 years) received electron beam tomography (EBT) scanning of the heart and a clinical examination. Clinical CAD was defined as a confirmed history of myocardial infarction (MI), angiographic stenosis > or =50%, Pittsburgh EDC Study physician-diagnosed angina, or ischemic electrocardiogram (ECG). CAC correlated with most CVD risk factors. CAC had 84 and 71% sensitivity for clinical CAD in men and women, respectively, and 100% sensitivity for MI or obstructive CAD. A CACS cut point of 400 was the most efficient coronary calcium correlate of CAD. In subjects with angina only, CAC sensitivity was 83% in men and 46% in women. In logistic regression, CAC, ECG R-R variation, peripheral vascular disease, and Beck Depression Inventory independently correlated with prevalent CAD in men and overall. Except for CAC, the same variables independently correlated with CAD in women, and age also entered the model. CAC was an independent correlate of MI or obstructive CAD in both sexes and was the strongest independent correlate in men, but CAC was not independently associated with angina and ischemic ECG in either sex. It is concluded that EBT-detected CAC is strongly correlated with CAD in type 1 diabetes-particularly in men.
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PMID:Coronary calcium in adults with type 1 diabetes: a stronger correlate of clinical coronary artery disease in men than in women. 1096 42

Amylin (AMY) is a 37 amino acid peptide cosecreted with insulin (INS) by pancreatic beta-cells and absent in type 1 diabetes, a condition frequently associated with osteopenia. AMY binds to calcitonin receptors, lowers plasma calcium concentration, inhibits osteoclast activity, and stimulates osteoblasts. In the present study, we examined the effects of AMY replacement on bone loss in a streptozotocin (STZ)-induced rodent model type 1 diabetes. Of 50 male Wistar rats studied, 40 were made diabetic with intraperitoneal STZ (50 mg/kg; plasma glucose concentrations > 11 mM within 5 days). Ten nondiabetic control (CONT) rats received citrate buffer without STZ. Diabetic rats were divided into four groups (n = 10/group) and injected subcutaneously with rat AMY (45 mg/kg), INS (12 U/kg), both (same doses), or saline (STZ; diabetic controls) once per day. After 40 days of treatment and five 24-h periods of urine collection for deoxypyridinoline (DPD), the animals were killed, blood was sampled, and femurs were removed. The left femur was tested for mechanical resistance (three-point bending). The right femur was tested for total, diaphyseal (cortical bone), and metaphyseal (trabecular bone) bone densities using dual-energy X-ray absorptiometry (DXA). Bone was ashed to determine total bone mineral (calcium) content. None of the treatments had any significant effect on femoral length and diameter. Untreated diabetic rats (STZ; 145+/-7N) had lower bone strength than did nondiabetic CONT (164+/-38; p < 0.05). Total bone mineral density (BMD; g/cm2) was significantly lower in STZ (0. 2523+/-0.0076) than in CONT (0.2826+/-0.0055), as were metaphyseal and diaphyseal densities. Diabetic rats treated with AMY, INS, or both had bone strengths and bone densities that were indistinguishable from those in nondiabetic CONT. Changes in bone mineral content paralleled those for total BMD (T-BMD). Plasma osteocalcin (OC) concentration, a marker for osteoblastic activity, was markedly lower in untreated diabetic rats (7. 6+/-0.9 ng/ml); p < 0.05) than in nondiabetic CONT (29.8+/-1.7; p < 0.05) or than in AMY (20.1+/-0.7; p < 0.05). Urinary DPD excretion, a marker for bone resorption, was similar in untreated and AMY-treated diabetic rats (35.0+/-3.1 vs. 35.1+/-4.4 nmol/mmol creatinine), intermediate in rats treated with INS (49.9+/-2.7), and normalized in diabetic rats treated with both agents (58.8+/-8.9 vs. 63.2+/-4.5 in CONT). Thus, in our STZ rat model of diabetic osteopenia, addition of AMY improved bone indices apparently by both inhibiting resorption and stimulating bone formation.
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PMID:Amylin and bone metabolism in streptozotocin-induced diabetic rats. 1134 42

Microalbuminuria (MA) is defined as persistent elevation of albumin in the urine, of 30-300 mg/day (20-200 microg/min). These values are less than the values detected by routine urine dipstick testing, which does not become positive until protein excretion exceeds 300-500 mg/day. Use of the albumin-to-creatinine ratio is recommended as the preferred screening strategy for all diabetic patients. MA is measured in spot morning urine obtained from the patient in the office and sent for measurement of both albumin and creatinine. A value above 0.03 mg/mg suggests that albumin excretion is above 30 mg/day and therefore MA is present. MA should be checked annually in everyone, and every 6 months within the first year of treatment to assess the impact in patients started on antihypertensive therapy. MA is an established risk factor for renal disease progression in type 1 diabetes and its presence is the earliest clinical sign of diabetic nephropathy. In addition, a number of studies suggest that MA is an important risk factor for cardiovascular disease and defines a group at high risk for early cardiovascular mortality in both type 2 diabetes and essential hypertension. MA also signifies abnormal vascular permeability and the presence of atherosclerosis. Among nondiabetic patients with essential hypertension, MA is associated with higher blood pressures, increased serum total cholesterol, and reduced serum high-density lipoprotein cholesterol. Thus, taken together these data support the concept that the presence of MA is the kidney's notice to the physician/patient that there is a problem with the vasculature. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or renal disease. This should be accomplished with antihypertensive agents that prevent the rise in MA and hence prevent development of proteinuria. Such agents are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and, to a lesser extent, Beta blockers, non-dihydropyridine calcium antagonists, and diuretics. In summary, the presence of MA is a marker of endothelial dysfunction and a harbinger of markedly enhanced cardiovascular risk. All patients with diabetes and/or hypertension should be screened for the presence of microalbuminuria with use of spot morning urine. To maximize prevention of MA development, the following goals should be instituted: 1) blood pressure should be maintained at less than 130/80 mm Hg and a low-salt, moderate-potassium diet instituted; 2) in diabetics, HbA1c should be kept at less than 7%; 3) in obese patients, a weight loss program should be implemented, with a goal BMI of less than 30; and 4) the physician and patient, working together, should maintain low-density lipoprotein cholesterol at less than 120 mg/dL, and less than 100 mg/dL if diabetes is present. (c)2001 by Le Jacq Communications, Inc.
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PMID:Microalbuminuria: what is it? Why is it important? What should be done about it? 1141 91

Localized lesions at the foot skeleton are a serious and well recognized complication of diabetes mellitus which may impair the clinical outcome of the patients remarkably. In contrast, the presence of a generalized bone disease or osteoporosis related to diabetes mellitus is less acknowledged and its clinical relevance is less obvious. This paper is a clinically focused review of the literature on osteoporosis related to diabetes mellitus. Due to the different pathogenesis of diabetes mellitus type 1 and type 2 it is not surprising that there is no uniform entity of diabetic osteopathy. The majority of clinical studies in subjects with diabetes mellitus type 1 showed a moderately decreased bone mass at the forearm, while bone mass at the femur or lumbar spine was either decreased or not different from non-diabetic controls. In patients with diabetes mellitus type 2 the risk of osteopenia is not as clear as in type 1 diabetes. Bone mineral density at the forearm in patients with type 2 diabetes mellitus was decreased, unchanged or even increased in comparison to controls, while bone mineral density at the vertebrae or femoral neck was either not significantly different or increased, but rarely decreased. The underlying mechanisms triggering changes in bone mass in patients with diabetes mellitus type 1 and type 2 are not well known. In most studies there was no consistent relationship between the metabolic control of diabetes and bone mineral density. Biochemical parameters of the calcium and bone metabolism showed no clear relationship to the bone mineral density measurements. From few bone histology studies in humans and experimental studies there is evidence that a decreased bone formation is one major mechanism leading to reduced bone mass in diabetics. Microangiopathy at the bone tissue was also discussed as a possible reason for diabetic osteopenia. It was shown that insulin and insulin like growth factors (IGF-1, IGF-2) have an influence on bone metabolism itself and other growth factors, cytokines and hormones may determine changes in diabetic bone metabolism. Recent findings suggest that leptin is involved in the regulation of osteoblast function and bone mass, which is of special interest in diabetes mellitus type 2. The clinical relevance of osteoporosis or osteopenia is determined by the increased risk for insufficiency fractures. Few studies found an increased fracture risk, especially in older women with type 1 diabetes mellitus, while others did not show an increased risk for fractures or even found a decreased rate of fractures in women with diabetes mellitus type 2. There is a need for further longitudinal studies, including the incidence and risk factors for osteoporotic fractures. In clinical routine the extent of diagnostic and therapeutic activities in patients with type 1 or type 2 diabetes mellitus in respect to generalized bone disease or diabetic osteopenia should be based on individual conditions and risk profile for osteoporosis.
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PMID:Diabetes mellitus a risk for osteoporosis? 1146 May 94

The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are still not well defined. We evaluated total bone mineral content (TBMC) and bone mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of 12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation scores (Z-scores) were determined by comparing our results to controls matched for age, sex and pubertal status. BMD and bone formation and resorption markers were determined at the beginning of the study and after one year of follow up. Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26 children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below the mean. Mean lumbar spine Z-score remained unchanged after one year of follow up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or TBMC between groups. No correlation was observed between lumbar spine BMD Z-scores and duration of IDDM or degree of diabetes control, as assessed by the mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our patients initially and after one year of follow up; however, no correlation was obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy-terminal propeptide of type 1 collagen values and levels of urinary cross-linked N-telopeptides of type 1 collagen in the diabetic children were significantly lower than those of the matched controls. Osteoblastic activity as assessed by serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided into males and females and into children with more than or less than 2 yr duration of diabetes since diagnosis, no differences between groups were found. These results suggest that insulin dependent diabetes in children is associated with low bone turnover resulting in a deficit in bone mass which may be manifested as osteopenia in the growing bone. This defect is already present in trabecular bone early on in the disease and seems not to be related to glycemic control.
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PMID:Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally. 1151 57

The aim of the study was to evaluate whether in diabetics with good metabolic control and without any diabetic complications, disturbances of calcium, phosphorus and magnesium metabolism or hormonal regulation (parathormone/calcitonin) were present, and if they depended on type of diabetes, duration time of diabetes, kind of hypoglycaemic treatment, sex or age of patients. 83 subjects were examined, including: 14 with type 1 diabetes mellitus, 49 with type 2 diabetes mellitus and 20 healthy persons. All tests were performed in standarized low-calcium diet conditions. In basal conditions both serum concentrations and daily urine excretion of calcium, phosphorus, magnesium were estimated. Oral and intravenous calcium load tests with simultaneous parathormone, calcitonin, calcium, magnesium and phosphorus concentrations estimation were done. The final conclusions were as follow: Both in type 1 diabetes mellitus and type 2 diabetes mellitus subjects with good metabolic compensation and without advanced diabetic complications a tendency to early disturbances of calcium-phosphorus metabolism is observed. Physiological hormonal control (parathormone/calcitonin) is preserved. Correlations between mineral metabolism and type of diabetes, duration time of diabetes, daily insulin dose, body mass index and sex are observed. Kind of hypoglycaemic treatment has only slight influence on the mineral metabolism.
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PMID:[Bone complication in diabetic subjects with good metabolic control and without any late complications: selected problems. Part I: calcium, phosphorus and magnesium metabolism]. 1160 76

Whereas individual research papers about antihypertensive treatment in diabetics might be somewhat confusing, the weight of the evidence strongly suggests that: 1) In patients with type 1 diabetes, it is advantageous to use angiotensin-converting enzyme (ACE) inhibitors as primary treatment. 2) In type 2 diabetics, aggressive blood pressure (BP) lowering is warranted and, the calcium antagonist controversy notwithstanding, all drugs appear to be similarly useful in reducing cardiovascular mortality. Specifically, in the Systolic Hypertension in Europe study, compared with placebo, a calcium antagonist dramatically reduced cardiovascular (CV) events in elderly diabetics. The Hypertension Optimal Treatment study showed that, using a calcium antagonist-based regimen, the degree of BP lowering determines the degree of CV event reduction. Furthermore, the United Kingdom Prospective Diabetes Study (UKPDS) did not find a difference in CV events reduction in patients treated with beta-blockers or with ACE inhibitors. In the UKPDS, the effect of BP lowering on reduction in CV events was more substantial than the degree of CV reduction by blood sugar lowering. 3) Both the CAPtopril Prevention Project (CAPPP) and the Heart Outcomes Prevention Evaluation (HOPE) studies found that treatment with an ACE inhibitor may be useful in reducing the incidence of new-onset type 2 diabetes mellitus. 4) Finally, insulin resistance, a precursor of diabetes mellitus and a strong predictor of future CV disease, is differentially affected by antihypertensive treatment. beta-Blockers and diuretics worsen insulin resistance, whereas alpha-adrenergic blockers and central imidazoline binding agents increase insulin sensitivity. The effect of ACE inhibitors and angiotensin blockers may also positively affect insulin resistance, but the results are not uniformly positive. It stands to reason that the differential effect of various drugs on insulin resistance and primary CV events may be clinically relevant particularly in the course of the long-term prevention of mild hypertension. All current trials investigate the effect of the treatment on secondary prevention of CV events among patients with advanced complicated diabetes and hypertension.
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PMID:Antihypertensive treatment of patients with diabetes and hypertension. 1172 89

Vitamin D receptor (VDR) polymorphism influences susceptibility to type 1 diabetes, but the association with type 2 diabetes is not clear. We investigated the association between VDR polymorphism and type 2 diabetes and metabolic syndrome in a community-based study of unrelated older adults without known diabetes. Oral glucose tolerance test (75 g), plasma glucose and insulin measurement, homeostasis model assessment (HOMA), and VDR genotyping were performed. The distributions of genotype frequencies of ApaI, BsmI, and TaqI polymorphism did not differ between persons with and without diabetes, but the frequency of aa genotype of ApaI polymorphism was marginally higher in persons with type 2 diabetes (P =.058). Fasting plasma glucose (P <.05) and prevalence of glucose intolerance (P <.05) were significantly higher in nondiabetic persons with aa genotype compared with those with AA genotype. The bb genotype of BsmI polymorphism was associated with insulin resistance as assessed by HOMA after adjustment for age, sex, body mass index (BMI), and calcium and vitamin D use in persons without diabetes (P <.05). Our research suggests that ApaI polymorphism may be associated with glucose intolerance independent of defective insulin secretion and BsmI polymorphism with insulin resistance in a nondiabetic Caucasian population.
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PMID:Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: the Rancho Bernardo Study. 1237 Aug 62

1,25(OH)2D3, the activated form of vitamin D, is well known for its effects on calcium and bone metabolism, but also non-classical effects on cells of the immune system were described, in vivo as well as in vitro. Structural analogues have been developed with less calcemic effects, but at least comparable immune effects. Our group showed that treatment with 1,25(OH)2D3 can protect the NOD mouse, the murine model for type 1 diabetes, from diabetes in primary, secondary and tertiary prevention. This effect is based on shifts in cytokine profiles (Thelper1 to Thelper2), that occur specifically for the autoantigens, and on enhanced sensitivity of the autoreactive T lymphocytes to apoptotic signals thus leading to a better elimination of these potentially dangerous cells. 1,25(OH)2D3 and its analogues can therefore be considered as interventions aimed at the prevention or treatment of human type 1 diabetes.
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PMID:[1,25-dihydroxyvitamin D3: the endocrine system meets the immune system]. 1199 3


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