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The aim of this cross-sectional study was to establish the prevalence of renal involvement and to identify associations with its most important possible risk factors in a group of patients with Type II diabetes mellitus, representative of the population living in Catalonia. One thousand two hundred and three patients (47% males, mean age: 61 +/- 6 years, diabetes duration 9 +/- 6 years) were studied. Overnight urine samples were collected to determine urinary albumin excretion (UAE). If UAE was > 15 micrograms/min, a new 24-h urine collection for UAE measurement to establish the existence of microalbuminuria (20-200 micrograms/min) or macroalbuminuria (> 200 micrograms/min) was obtained. Clinic and metabolic evaluations were also performed. The prevalence (%) of microalbuminuria, macroalbuminuria and hypertension were, respectively, 23. 1, 5.4 and 42. In comparison with normoalbuminurics, patients with microalbuminuria were predominately male (P < 0.03), with a significantly higher systolic (P < 0.001) and diastolic (P < 0.001) blood pressure and body mass index (P < 0.001). The prevalence of smokers (former + current) was higher in patients with microalbuminuria (43 vs 32%, P < 0.025). Moreover, patients with nephropathy had more prevalence of retinopathy (P < 0.001), neuropathy (P < 0.001), peripheral angiopathy (P < 0.001) and coronary disease (P < 0.001). The prevalence of microalbuminuria in Type II diabetes in Catalonia is similar to that observed in other european countries. The existence of microalbuminuria is associated with several diabetic complications, as well as tobacco consumption and obesity.
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PMID:Epidemiology of renal involvement in type II diabetics (NIDDM) in Catalonia. The Catalan Diabetic Nephropathy Study Group. 885 4

Various types of microcirculation disturbances have been described in the course of systemic diseases, hypertension, diabetes, obesity, and the so-called "idiopathic oedema" syndrome. This article summarizes the relevant microcirculatory disorders associated with diabetes and their pathophysiology. These functional disorders occur before or in association with anatomical lesions of diabetic microangiopathy. Increased capillary permeability to albumin is frequently observed in diabetes. In a placebo-controlled trial, Daflon 500 mg, a purified, micronized, flavonoidic fraction, significantly improved this disorder. Patients complaining of an oedematous syndrome almost always have an increased extracellular fluid volume, probably largely due to increased capillary permeability. Diabetes and "idiopathic oedema" therefore constitute two examples of the major clinical implications of impaired microcirculation.
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PMID:Clinical implications of impaired microcirculation. 891 61

It has been suggested that obesity is associated with an altered rate of gastric emptying, and that there are also sex differences in gastric emptying. The results of earlier studies examining gastric emptying rates in obesity and in males and females have proved inconsistent. The aim of this study was to investigate the influence of obesity and gender on gastric emptying, by extending conventional evaluation methods with Kaplan-Meier plots, in order to assess whether these factors have to be accounted for when interpreting results of scintigraphic gastric emptying tests. Twenty-one normal-weight volunteers and nine obese subjects were fed a standardised technetium-99m labelled albumin omelette. Imaging data were acquired at 5- and 10-min intervals in both posterior and anterior projections with the subjects in the sitting position. The half-emptying time, analysed by Kaplan-Meier plot (log-rank test), were shorter in obese subjects compared to normal-weight subjects and later in females compared to males. Also, the lag-phase and half-emptying time were shorter in obese females than in normal females. This study shows an association between different gastric emptying rates and obesity and gender. Therefore, body mass index and gender have to be accounted for when interpreting results of scintigraphic gastric emptying studies.
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PMID:Gastric emptying of solids in humans: improved evaluation by Kaplan-Meier plots, with special reference to obesity and gender. 892 8

Neoadjuvant chemotherapy produces high response rates in squamous cell carcinoma of the head and neck without increasing the survival time. Furthermore authors have observed a death rate of about 5% (up to 10%) during chemotherapy. A series of patients with an oro- or hypo-pharynx cancer, were retrospectively divided into two groups on the basis of a short (< or = 2 months) or long (> or = 2 years) survival time. Clinical, tumoral and usual biological data from either group were compared. By univariate analysis, obesity index, hemoglobin, albumin concentrations and mononuclear cell counts were lower in patients with a short survival time compared with those in the other group. On the contrary, polymorphonuclear cell and platelet counts were higher. Infection appeared to be more frequent for patients with a poor prognosis without being entirely responsible for early death. By multivariate analysis, obesity index and platelet count were both independent variables associated with prognosis. These results call for further investigation of cardiac function, inflammatory, nutritional and immunological status of patients with squamous cell carcinoma of the head and neck who were given initial chemotherapy, particularly Cisplatin and Fluorouracil.
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PMID:Early death during initial chemotherapy of squamous cell carcinoma of the oro- or hypopharynx. 906 95

In 97 IDDM and 64 NIDDM patients aged under 65 years, we evaluated the relationship between autonomic neuropathy (AN) and retinopathy, nephropathy, glycemic control and cardiovascular risk factors. Diabetes duration and HbA1 were significantly higher and body mass index was significantly lower in IDDM patients with AN compared to those without. In NIDDM only age was significantly higher in neuropathic patients. AN was associated with retinopathy in both IDDM (chi2 = 10, P < 0.03) and NIDDM patients (chi2 = 14, P < 0.007), while only in IDDM albumin excretion was significantly higher in patients with AN. Blood pressure (BP) was significantly higher in both IDDM and NIDDM patients with AN compared to those without. There were no differences in smoking and serum lipids between patients with and those without AN. We performed a multiple regression analysis using autonomic score, index of cardiovascular tests impairment, as the dependent variable and age, diabetes duration, body mass index, HbA1, albumin excretion, cholesterolemia, triglyceridemia, systolic BP, and retinopathy as independent variables. With this model in IDDM autonomic score was only related to body mass index (r = -0.29, P < 0.05), to HbA1 (r = 0.46, P < 0.001), and to systolic BP (r = 0.24, P < 0.05), while in NIDDM it was only related to systolic BP (r = 0.54, P < 0.001). In conclusion, AN was related to age in NIDDM, and to diabetes duration and glycemic control in IDDM. AN was associated with retinopathy, with nephropathy (only in IDDM), and with BP levels, but not with dyslipidemia, smoking, or obesity. Excess mortality rate observed in diabetic AN cannot be referred to an association with cardiovascular risk factors.
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PMID:Autonomic neuropathy and cardiovascular risk factors in insulin-dependent and non insulin-dependent diabetes. 906 69

To investigate the association between insulin resistance and diabetic nephropathy, peripheral insulin sensitivity indices (M/I values) were evaluated via euglycemic-hyperinsulinemic clamp in 45 non-obese, non-insulin-dependent diabetic (NIDDM) subjects. The patients were divided into four groups: 18 with normoalbuminuria (urinary albumin excretion rate [AER] < 30 mg/24 h, stage I), 10 with microalbuminuria (30 < or = AER < or = 300 mg/24 h, stage II), seven with overt proteinuria (AER > 300 mg/24 h, stage III), and 10 with uremia (serum creatinine levels > 2.0 mg/dL, stage IV). There were no significant differences in age, body mass index (BMI), fasting plasma glucose, or hemoglobin A1c (HbA1c) among the four groups. No significant difference in M/I values was seen between stage I and stage II (6.30 +/- 0.73 and 5.95 +/- 0.85 mg/kg/(min per microU/mL) x 100, respectively). M/I values in the stage I and stage II groups were strongly correlated with BMI (r = -.790, P = .0001 and r = -.785, P = .007, respectively). M/I values in the stage III group (4.53 +/- 0.51) were lower than in the stage I group, although not significantly so. M/I values in the stage IV group (3.16 +/- 0.37) were significantly lower than in the stage I group (P = .025). In multiple regression analysis with a model in which age, sex, BMI, HbA1c, and creatinine clearance (Ccr) were included as independent variables, BMI and Ccr were demonstrated to be significant and independent contributors to insulin sensitivity indices as the dependent variable (beta = -0.716 and beta = 0.272, respectively, R2 = .564, P < .0001). In conclusion, the present cross-sectional study demonstrated in non-obese NIDDM patients with nephropathy that microalbuminuria did not affect peripheral insulin resistance, but uremia did, as in nondiabetic patients, and that the peripheral insulin resistance was significantly contributed to by the degree of obesity and uremia.
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PMID:Insulin resistance in non-obese, non-insulin-dependent diabetic patients with diabetic nephropathy. 928 89

Elevated insulin levels may explain part of the increased risk of endometrial cancer observed in obese postmenopausal women. Circulating sex hormones and fasting C-peptide levels were measured in sera obtained from 165 postmenopausal endometrial cancer cases accrued between June 1, 1987, and May 15, 1990, from hospitals in Chicago, Illinois; Hershey, Pennsylvania; Irvine and Long Beach, California; Minneapolis, Minnesota; and Winston-Salem, North Carolina, and 180 community and hysterectomy controls. Women with a personal history of diabetes were excluded. Among controls, C-peptide was positively correlated with body mass index (BMI) ((r = 0.44), waist-to-thigh circumference ratio ((r = 0.24), estrone ((r = 0.18), and estradiol ((r = 0.28) (albumin-bound (r = 0.45), and free (r = 0.37)) and negatively correlated with sex hormone-binding globulin (r = -0.48). In age-adjusted analyses, the odds ratios and 95% confidence intervals for tertiles of C-peptide and endometrial cancer were, from lowest to highest: 1.0 (reference), 0.78 (95% confidence interval (CI) 0.43-1.4), and 2.2 (95% CI 1.3-3.7). Further adjustment for BMI substantially attenuated the odds ratios for the highest tertile of C-peptide (odds ratio = 1.2, 95% CI 0.63-2.1), and adjustment for body mass index and other risk factors for endometrial cancer eliminated the association (odds ratio = 1.0, 95% CI 0.55-2.0). In contrast, adjustment for C-peptide had little influence on the magnitude of the positive associations between body mass index (odds ratio for highest vs. lowest tertile, without and with adjustment for C-peptide = 4.1 (95% CI 2.3-7.5) and 3.7 (95% CI 1.9-7.1), respectively) or several steroid hormones and endometrial cancer. These data are not consistent with the hypothesis that the effect of obesity on endometrial cancer risk is mediated through high insulin levels.
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PMID:Insulin and endometrial cancer. 929 May 8

Both microalbuminuria and insulin resistance are present at some stage in the natural history of non-insulin-dependent diabetes mellitus (NIDDM). Microalbuminuria predicts both progression to endstage renal disease and an increase in cardiovascular mortality compared to diabetic patients without microalbuminuria. Conversely, microalbuminuria is not a strong predictor of either renal or cardiovascular mortality in hypertensive nondiabetic subjects. This difference in risk may relate to the presence of glycated albumin in patients with diabetes. Glycation of albumin occurs because of persistent hyperglycemia. Glycated albumin is directly toxic to both renal and vascular tissue through stimulation of reactive oxygen species by both renal and immune protective cells. Blunting the rise in microalbuminuria with either aggressive blood glucose control or angiotensin-converting enzyme (ACE) inhibition, early in the course of the disease, markedly reduces renal mortality. In contrast to microalbuminuria, which is a reflection of renal injury, insulin resistance is a genetically determined problem that directly relates to peripheral glucose utilization. In most cases, insulin resistance is phenotypically expressed as diabetes as a result of environmental factors such as obesity. Insulin resistance is associated with an increased risk for development of both hypertension and NIDDM as well as atherosclerosis. Diabetic or hypertensive subjects with insulin resistance have an increased risk of cardiovascular but not renal mortality. Sustained weight loss is the best way to reduce insulin resistance and arterial pressure. Additionally, alpha blockers, more than other antihypertensive agents reduce insulin resistance. This class of drugs, however, has not been shown to reduce either microalbuminuria or overall cardio-renal mortality.
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PMID:Predictors of renal and cardiovascular mortality in patients with non-insulin-dependent diabetes: a brief overview of microalbuminuria and insulin resistance. 936 78

We review some of the effects that insulin exerts on glomerular and tubular functions. In healthy subjects, insulin has little or no effect on renal hemodynamics, glomerular filtration rate, or permeability to albumin. In patients with noninsulin-dependent diabetes, hyperinsulinemia selectively increases urinary albumin excretion. In vivo, euglycemic hyperinsulinemia is associated with reduced urinary sodium excretion both under conditions of forced and normal diuresis. Whether the principal site of this action is the proximal or distal tubule remains somewhat controversial. The effect, however, is not mediated by insulin-induced hypokalemia and antikaliuresis, as it is still observed when plasma potassium concentrations and urinary potassium excretion are maintained. Hyperglycemia potentiates insulin antinatriuresis through an effect on the proximal tubule (sodium-glucose cotransport). Insulin antinatriuresis is accompanied by a reduction in the urinary excretion of uric acid. Both the antinatriuretic and antiuricosuric effect of insulin are preserved in states of insulin resistance of glucose metabolism (obesity, diabetes, essential hypertension). Thus, in insulin resistant individuals compensatory hyperinsulinemia imposes a chronic antinatriuretic and antiuricosuric pressure on the kidney. This may provide an explantation for the clustering of insulin resistance with hypertension and hyperuricemia.
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PMID:Renal effects of insulin in man. 937 25

Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertriglyceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated acute-phase/stress reactants (the innate immune system's response to environmental stress) and their major cytokine mediator (interleukin-6, IL-6) are associated with NIDDM and syndrome X, and may thus provide a unifying pathophysiological mechanism for these conditions. Two groups of Caucasian subjects with NIDDM were studied. Those with any 4 or 5 features of syndrome X (n = 19) were compared with a group with 0 or 1 feature of syndrome X (n = 25) but similar age, sex distribution, diabetes duration, glycaemic control and diabetes treatment. Healthy non-diabetic subjects of comparable age and sex acted as controls. Overnight urinary albumin excretion rate, a risk factor for cardiovascular disease, was also assayed in subjects to assess its relationship to the acute-phase response. Serum sialic acid was confirmed as a marker of the acute-phase response since serum concentrations were significantly related to established acute-phase proteins such as alpha-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, alpha-1 acid glycoprotein, IL-6 and urinary albumin excretion rate amongst the three groups, with the lowest levels in non-diabetic subjects, intermediate levels in NIDDM patients without syndrome X and highest levels in NIDDM patients with syndrome X. C-reactive protein and cortisol levels were also higher in syndrome X-positive compared to X-negative patients and serum amyloid A was higher in both diabetic groups than in the control group. We conclude that NIDDM is associated with an elevated acute-phase response, particularly in those with features of syndrome X. Abnormalities of the innate immune system may be a contributor to the hypertriglyceridaemia, low HDL cholesterol, hypertension, glucose intolerance, insulin resistance and accelerated atherosclerosis of NIDDM. Microalbuminuria may be a component of the acute-phase response.
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PMID:NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. 2212 8


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