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Query: UMLS:C0011849 (diabetes)
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To better understand the pathophysiology of glucose intolerance secondary to iron overload in patients with thalassemia major, we performed tolbutamide-modified frequently sampled iv glucose tolerance tests (FSIGTs) in 10 thalassemic patients (6 males and 4 females; 21.7 +/- 1.2 yr old; body mass index, 19.7 +/- 0.6 kg/m2) and 10 healthy controls (5 males and 5 females; 22.4 +/- 1.3 yr; body mass index, 20.6 +/- 0.5 kg/m2). Insulin secretion and action were quantified by application of the minimal model of glucose kinetics and the combined model of insulin and C-peptide kinetics to the FSIGT data. The insulin sensitivity index was significantly lower in thalassemia patients [72 +/- 12 min-1(nmol/mL)] compared to controls [158 +/- 21 min-1(nmol/mL); P = 0.0026]. The integrated insulin response during the FSIGT was significantly greater in thalassemia patients than in controls after tolbutamide injection (P = 0.042). The difference in insulin levels was apparently due to reduced hepatic insulin extraction in thalassemia (78 +/- 2% vs. 68 +/- 3%; P = 0.0251). Seven of the 10 thalassemia patients were studied prospectively at 6-month intervals for 6-12 months. Repeated measures analysis of variance indicated that across a 6-month interval, there was a decrease in the total integrated insulin response (P = 0.002), with no change in insulin sensitivity (P = 0.86). In conclusion, patients with thalassemia major have significant insulin resistance, which may be compensated for by an elevated circulating insulin level. The elevated insulin level in response to tolbutamide appears to be due to reduced hepatic extraction of insulin and not to an enhanced insulin secretory response. Over time, patients with thalassemia experience a reduction in their circulating insulin levels. Persistent insulin resistance along with a progressive reduction in circulating insulin levels may lead to glucose intolerance and diabetes mellitus, which have a high prevalence in patients with thalassemia major.
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PMID:Factors determining glucose tolerance in patients with thalassemia major. 834 55

Contrasting information has been reported concerning the course of renal function in NIDDM with hypertension alone or in association with renal damage. The aim of the present study was to elucidate the course of the glomerular filtration rate (GFR) in hypertensive NIDDM patients during antihypertensive therapy. Furthermore, we compared the effects of ACE inhibitors (cilazapril, Inibace, Roche, Milan, Italy) and Ca(2+)-channel blockers (amlodipine, Norvasc, Pfizer, Rome, Italy). Of the hypertensive NIDDM patients attending the outpatient's clinic of the internal medicine departments of the University of Padova and Sassari, 44 participated in the present study. Of these patients, 26 were normoalbuminuric and 18 microalbuminuric. They were randomly treated with either cilazapril or amlodipine. The target of antihypertensive treatment was a value < 140 mmHg for systolic and 85 mmHg for diastolic blood pressure (BP). Microalbuminuria was defined as an albumin excretion rate (AER) between 20 and 200 micrograms/min. GFR was measured by plasma clearance of 51Cr-labeled EDTA at baseline and every 6-12 months during a 3-year follow-up interval. A significant decrease was observed in the values of GFR, AER, and systolic and diastolic BP in normoalbuminuric and microalbuminuric patients during antihypertensive therapy. The GFR fall in the overall population of NIDDM patients was significantly and inversely related to the decrease of mean BP (diastolic + 1/3 pulse pressure) (r = -0.80, P < 0.0001) but not to that of HbA1c, triglycerides, and BMI. The GFR decline (mean +/- SE) per year in the normoalbuminuric patient was 2.03 +/- 0.66 ml.min-1 x 1.73 m-2 (95% CI 0.92-3.17) during cilazapril and 2.01 +/- 0.71 ml.min-1 x 1.73 m-2 (95% CI 0.82-3.11) during amlodipine therapy. The GFR decline per year in the microalbuminuric patient was 2.15 +/- 0.69 ml.min-1 x 1.73 m-2 (95% CI 0.86-3.89) during cilazapril and 2.33 +/- 0.83 ml.min-1 x 1.73 m-2 per year (95% CI 1.03-3.67) during amlodipine therapy. Cilazapril and amlodipine lowered AER to a similar extent in normoalbuminuric and microalbuminuric patients. No significant changes were observed concerning other clinical and biochemical features between the two antihypertensive therapies and particularly HbA1c, BMI, triglycerides, and cholesterol plasma values. These results support the tenet that arterial hypertension plays a pivotal role in contributing to renal damage in NIDDM, even when AER is normal. However, the degree of BP control, with both cilazapril and amlodipine, can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy.
Diabetes 1996 Feb
PMID:Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. 854 68

The aim of this study was to analyse the influence of patient characteristics on delay between onset of symptoms and hospital admission (patient delay) in acute myocardial infarction, and especially to assess the impact of risk factors for acute myocardial infarction on patient delay. A group of 6676 consecutive patients with enzyme-confirmed acute myocardial infarction, admitted alive to 27 Danish hospitals over a 26 month period from 1990 to 1992, were studied. Due to missing information on delay or in-hospital acute myocardial infarction 698 patients were excluded, leaving 5978 patients for analysis. Mean patient delay was 9.1 h, median delay 3.25 h (5 to 95 percentiles: 0.67-40.0 h). Thirty-four percent were admitted within the first 2 h, 68% within 6 h and 81% within 12 h of onset of symptoms. In multivariate logistic regression analysis, a greater than 2 h patient delay was independently associated with male gender (odds ratio (OR) = 0.809, P = 0.003), increased age (P = 0.0001), diabetes mellitus (OR = 1.269, P = 0.03), left ventricular systolic function (wall motion index) (P = 0.02), onset from midnight to 0600h (OR = 1.434, P = 0.0001), onset on a weekday (OR = 0.862, P = 0.04), history of angina pectoris (OR = 1.198, P = 0.02), chest pain as initial symptom (OR = 1.293, P = 0.02), ventricular fibrillation (OR = 0.562, P = 0.0001), ventricular tachycardia (OR = 0.620, P = 0.0001), Killip class > or = 3 (OR = 0.709 P = 0.002), presence of ST elevation (OR = 0.810, P = 0.01) and ST depressions (OR = 0.847, P = 0.01). All these variables, except history of diabetes mellitus, angina pectoris, and chest pain as an initial symptom were also associated with a delay of more than 6 h. Thrombolytic therapy was administered to 55.8% of patients admitted within 2 h of an acute myocardial infarction, 48.5% of patients admitted within 2-6 h, 31.5% of patients admitted after 6-12 h and 11.9% of patients arriving later than 12 h after start of symptoms. CONCLUSION. Patient delay continues to be disappointingly long. This also applies for patients at a high risk of acute myocardial infarction (notably those with a history of diabetes mellitus and angina pectoris).
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PMID:Determinants of delay between symptoms and hospital admission in 5978 patients with acute myocardial infarction. The TRACE Study Group. Trandolapril Cardiac Evaluation. 873 7

Conventional treatment of obese noninsulin dependent diabetes mellitus (NIDDM) patients is often unsatisfactory. In this study the efficacy of Modifast, a commercial very low calorie diet (VLCD), was evaluated in a population of obese poorly controlled NIDDM patients. The mechanisms of action of VLCD in these patients were also studied by comparing: (i) Plasma insulin and glucose profiles after a VLCD and an isocaloric mixed meal and (ii) plasma amino acid levels, both at baseline and after four weeks of VLCD treatment. A total of 14 obese NIDDM patients (M/F 7/7. median body mass index (BMI) 38.7 kg-2, interquartile range (IQ) 34.7-46.5 kg-2, waist circumference 116 cm, IQ 106-139 cm, insulin treated 7/14) with poor diabetic control (HbA1c 8.6%, IQ 7.8-10%) were studied. Patients were given a VLCD (425 kcal/day) for 12 weeks. At baseline, VLCD and isocaloric meal tests were performed on consecutive mornings. Fasting plasma amino acid levels were also determined at baseline and after 4 weeks of VLCD treatment. Weight, waist circumference, HbA1c, blood pressure, fasting plasma insulin, total cholesterol and triglyceride levels all fell significantly following VLCD treatment. Insulin therapy was able to be ceased in the seven insulin treated patients. Oral hypoglycaemic agent dosage fell from a median of eight (IQ 6-12) to two (IQ 0-8) tablets per day (P = 0.03) in patients initially on this form of therapy. Insulin secretion was higher after VLCD than isocaloric meal (P = 0.04). Fasting plasma alanine level fell from 512.0 (IQ 412.0-563.0) to 374.0 (IQ 342-472.0) mumol/l (P = 0.04) following VLCD treatment. In conclusion, the short term use of a VLCD is very effective in rapidly improving glycaemic control and promoting substantial weight loss in obese NIDDM patients. Moreover, a VLCD diet increases insulin secretion and reduces substrate for gluconeogenesis. Thus, VLCD treatment may improve glycaemic control by factors more than caloric restriction alone.
Diabetes Res Clin Pract 1997 May
PMID:Very low calorie diet (VLCD): a useful alternative in the treatment of the obese NIDDM patient. 922 94

Common late complications after esophagectomy and gastric tube reconstruction for esophageal carcinoma are symptomatic, benign fibrotic stenoses of the cervical anastomosis, which require dilatation. Since the prognosis of esophageal carcinoma still remains poor, bad functional results such as dysphagia affect quality of life. In a retrospective analysis, our patients were evaluated with regard to the underlying effects of cervical anastomotic stenosis after esophagectomy and gastric tube reconstruction. From 1 January 1989 to 31 July 1995, 173 patients with carcinoma of the esophagus were operated in our institution. Transhiatal esophageal dissection was performed in 133 patients; 40 patients underwent transthoracic en bloc resection. The 30-day mortality rate was 7.5% (13 patients). Postoperative fibrotic stenosis of the cervical anastomosis requiring dilatation occurred in 36.4% (63 patients) 6-12 weeks after operation. Fibrotic stenosis of the cervical anastomosis did not develop in 97 patients. There was a significant difference concerning the incidence of anastomotic leaks within both groups: whereas in 23.8% of the 63 patients who developed a fibrotic stricture of the cervical anastomosis an anastomotic leak preceded this event (P < 0.001), no anastomotic leak occurred in the group of 97 patients with normal healing of the cervical anastomosis. In addition, significantly (P < 0.01) more patients (37.5%, n = 23) with preexisting diabetes mellitus could be found among the 63 patients who developed a fibrotic stricture of the cervical anastomosis, in contrast to the 97 patients without anastomotic stenosis.
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PMID:[Cervical anastomotic stenosis after gastric tube reconstruction in esophageal carcinoma. Evaluation of a patient sample 1989-1995]. 932 13

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.
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PMID:Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients. A prospective study. 940 27

A case-control study of coronary heart disease (CHD) was conducted in Oporto, Portugal. The cases series consisted of 100 consecutive patients with first time acute myocardial infarction who were admitted to the Coronary and Intermediate Care Units of a major teaching hospital. The community controls were 198 individuals without evidence of CHD by the Rose questionnaire and electrocardiography, selected by random digit dialing, with a participation rate of 70%. Data was collected by trained interviewers using a structured questionnaire and blood samples were obtained for selected laboratory data. The main analysis was made through unconditional logistic regression with calculations of odds ratios (OR). Age, OR: 1.5 (95% CI: 0.8-2.9), male gender, OR: 6.7 (3.6-12.3), family history of premature CHD, OR: 2.4 (1.4-4.3), diabetes, OR: 3.4 (1.6-7.4), antecedents of hypertension, OR:1.9 (1.1-3.1), history of high cholesterol levels, OR: 2.3 (1.4-3.9), high levels of physical activity, OR: 2.0 (0.9-4.1) and tobacco smoking, OR: 8.3 (3.8-18.5) were significant risk factors of acute myocardial infarction. After controlling for demographic variables and for the mutual confounding effects of the risk factors, the investigated factors that remained significantly associated with the risk of developing acute myocardial infarction were male gender, OR: 17.3 (4.8-62.3), family history of CHD, OR: 3.6 (1.4-9.6), diabetes, OR: 4.2 (1.0-18.1), high cholesterol levels OR: 2.7 (1.2-6.1) and smoking habits, OR: 7.7 (1.8-32.4). A negative association with high education levels was significant after controlling for all the variables, OR: 0.01 (0.01-0.5).
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PMID:[Risk factors for myocardial infarct: a case-control study in Oporto, Portugal]. 940 36

Insulin modulates the differentiation and synthetic activity of osteoblasts, but its mechanisms of action are not fully understood. Because ascorbate also influences osteoblast differentiation and is a cofactor for collagen synthesis, we examined the effects of insulin on the transport and metabolism of vitamin C in osteoblastic cells. UMR-106 rat osteoblast-like cells accumulated ascorbate intracellularly when incubated with dehydroascorbic acid (DHAA; oxidized vitamin C). Insulin increased the intracellular concentration of ascorbate derived from DHAA and also increased the initial rates of uptake of DHAA and 2-deoxyglucose, but not that of ascorbate. A half-maximal effect on DHAA uptake was observed with approximately 100 pM insulin, whereas insulin-like growth factor I (IGF-I) was less potent. Preincubation with insulin for 6-12 h was required for stimulation, similar to the period needed for increased expression of facilitative hexose transporters (GLUT). DHAA uptake was inhibited by the GLUT antagonist cytochalasin B as well as by the GLUT substrates D-glucose and 2-deoxyglucose, whereas L-glucose and fructose had no effect. We conclude that insulin and IGF-I stimulate osteoblastic uptake of DHAA through facilitative hexose transporters. The relative potency of insulin in stimulating DHAA uptake is consistent with mediation by insulin receptors. DHAA is reduced to ascorbate within osteoblasts, maintaining a high intracellular concentration of ascorbate available for collagen synthesis. Impaired uptake of DHAA may contribute to the osteopenia associated with type I diabetes. In addition, cytotoxic levels of DHAA may accumulate in the extracellular fluid due to decreased transport activity and competitive inhibition by elevated concentrations of glucose.
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PMID:Insulin stimulates vitamin C recycling and ascorbate accumulation in osteoblastic cells. 942 97

Nephropathy is the major life-threatening complication of insulin-dependent diabetes mellitus (IDDM). The clinical syndrome is characterized by persistent albuminuria (greater than 300 mg day), a rise in arterial blood pressure, and a relentless decline in glomerular filtration rate leading to end-stage renal failure. The availability of a radioimmunoassay for detecting albumin in low concentrations in urine has allowed the study of urinary albumin excretion rates in diabetics well before clinically persistent proteinuria develops. An albumin excretion rate greater than that in normal subjects and lower than that in macroalbuminuric subjects is called microalbuminuria (range 20-200 microg/min or 30-300 mg/24 h). Although recent studies have challenged the predictive value of microalbuminuria for later development of overt diabetic nephropathy, albumin excretion rate in the microalbuminuric range and its tracking (i.e. annual increase) are still considered reliable markers for prediction of later overt diabetic kidney disease. Overnight urinary collection is preferred for calculation of the rate of albumin excretion, but may be difficult to perform precisely. The albumin:creatinine ratio of the first morning urine sample is a reliable screening method: the microalbuminuric range is considered to be 2.5-25 mg/mmol or 30-300 mg/g (3.5 mg/mol has been proposed as lower limit in females because of their lower creatinine excretion). Irrespective of the procedure used, at least two samples over a 3-6-month period should test positive before microalbuminuria is confirmed and 'persistent microalbuminuria' defined. If the albumin excretion rate is persistently in the microalbuminuric range it is of crucial importance to define strategies and carry out interventions for prevention of decline in kidney function. The goal of achieving the best glycaemic control as early as possible in as many IDDM patients as is safely possible is particularly important in microalbuminuric patients. Although it is unsafe to reduce dietary protein intake drastically, particularly in children and adolescents, moderate decrease of protein intake (i.e. 0.9-1.1/g/kg day) is advisable in diabetic patients from the very beginning of the disease. Timely treatment with an angiotensin-converting enzyme inhibitor, independently of rise in arterial blood pressure, should be considered if improvement of glycaemic control and moderate decrease of dietary protein intake for 6-12 months have failed to reduce the albumin excretion rate. Screening programmes for microalbuminuria and early intervention can substantially modify the natural history of diabetic renal involvement and disease and possibly reduce the incidence of end-stage renal failure.
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PMID:The importance of microalbuminuria as an indicator of incipient diabetic nephropathy: therapeutic implications. 945 92

The recent demonstration of ectopic production of human placental lactogen (PL) in the human testis and ovary prompted us to reassess its role under non-pregnant physiological and pathological conditions. Possible physiological hPL concentrations and potential age-related changes in the sera of healthy young and elderly individuals (n = 75) selected according to the SENIEUR-protocol were investigated by a highly sensitive (detection limit: 2 pg/ml) and specific (cross-reactivity with prolactin and human growth hormone (hGH) of less than 0.001% and 0.0001%, respectively) monoclonal antibody-based time-resolved fluoroimmunoassay (IFMA) established in our laboratory. All individuals, even the aged probands (mean age: 72 +/- 3a), had hPL-levels below 20 pg/ml, in contrast to glycoprotein hormones, such as luteinizing hormone or human chorionic gonadotropin (hCG). To determine the significance of hPL as a tumour marker, serum samples of 12 testicular cancer patients with highly elevated levels of holo-hCG (mean: 42.490 ng/ml) at diagnosis were followed over 6-12 months and analysed with the hPL-IFMA. Elevation of hPL was seen in 10 patients, but the respective levels were 2-3 orders of magnitude smaller than those of holo-hCG and returned earlier to undetectable values. These in vivo data were compared to the hPL secretion pattern of the choriocarcinoma cell lines JAR and BeWo in vitro. In tissue culture supernatants of the two cell lines hPL was detected only in JAR cells, whereas both cell lines secreted holo-hCG. In conclusion, the fact that hPL is not physiologically present in peripheral blood but is produced ectopically in the human testis and ovary suggest auto/paracrine functions of this molecule. The significance of hPL as a tumour marker for patients with testicular cancer is limited as it provides no additional information to holo-hCG.
Exp Clin Endocrinol Diabetes 1998
PMID:Reassessment of the role of human placental lactogen in physiological non-pregnant and pathological conditions. 951 62


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