Search

Microalbuminuria (MA) is an important early sign of diabetic nephropathy. Hyperfiltration and impaired filtration in relation to albuminuria has been well investigated in diabetic subjects. This study tested the hypothesis that an increased urinary albumin excretion (UAE) is associated with renal functional abnormalities also in nondiabetic subjects. The relation between UAE and creatinine clearances (Ccr) in 7728 nondiabetic subjects was studied. Subjects were divided in four groups according to UAE (mg/24 h): 0 to 15 (control), 15 to 30 (high-normal albuminuria [HNA]), 30 to 300 (MA), >300 (macroalbuminuria). An elevated filtration and a diminished filtration were defined as a Ccr exceeding or below 2x the SD of the control group corrected for age and gender. Ccr followed a parabolic trend, with a higher Ccr in the HNA as compared with control and a lower Ccr in the MA and macroalbuminuria group as compared with HNA. With each increasing UAE level, male sex, age, body mass index, minimal waist circumference, systolic and diastolic BP, plasma glucose, and a positive family history for diabetes all followed a significant linear increasing trend (P < 0.001). After adjustment for age, gender, body mass index, plasma glucose, a positive family history for diabetes, systolic and diastolic BP, antihypertensive medication, and smoking in a multivariate analysis, HNA and MA were independently associated with an elevated filtration (RR 1.8 [95% confidence interval, 1.30 to 2.51] and 1.7 [1.17 to 2. 45]). Macroalbuminuria was independently associated with a diminished filtration (4.3 [range, 1.97 to 9.36]). In conclusion, an elevated UAE might be an important and early sign for progressive renal function loss in a nondiabetic population.

The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, We unknown. We carried out a 6 mouths study in 24 GH-deficient adults who were randomized to placebo (n 8), low dose GH (1 U daily, n = 8), and high dose GH (2 U daily, n = 8), followed by a 6 months open extension study with high dose GH (1 dropout), No significant changes in plasma lipoproteins, LCAT, CETP, and PLTP activities, cholesterol esterification (EST) and cholesteryl ester transfer (CET) were observed after placebo. After 6 months of GH (combined data, n = 24), very low + low density lipoprotein (VLDL + LDL) cholesterol (P

In January 1997 a drug from a new pharmacological class, the thiazolidinediones, became available: troglitazone. Troglitazone indirectly enhances peripheral insulin sensitivity. In this way it lowers the levels of both glucose and insulin. Troglitazone also has a lowering effect on the levels of triglycerides. In clinical trials only mild side effects had been observed. Therefore, troglitazone seemed a promising drug. Recently, however, it became clear that troglitazone could cause liver dysfunction in some patients. Although this side effect is reversible in most cases, six deaths have been described due to liver damage. Troglitazone was to be introduced in Europe in 1998 but registration procedures and clinical trials have been stopped because of its side effects on the liver. In the United States and Japan troglitazone is still being used, albeit with extra precautions. Troglitazone is a valuable addition to the arsenal of antidiabetic drugs for type 2 diabetes. It can be particularly useful, both as an additive and as a replacement, in patients for whom metformin is not suitable because of contraindications or side effects. The risk of severe liver dysfunction is a reason to reserve troglitazone as a second-line drug. (C) 1999 Published by Elsevier Science B.V. All rights reserved.

To investigate whether there is a circadian regulation of insulin secretion, rats were adapted to a feeding regimen of six meals equally distributed over 24 h. Under these conditions basal glucose and insulin levels increased during the light phase and decreased during the dark phase. Maximal blood glucose responses were fairly similar during the six different meals, but glucose increments were clearly delayed during the last two meals consumed during the light period. Insulin increments were highest during the dark phase and clearly diminished during the second half of the light phase. This situation was reversed when the scheduled meals were replaced by i.v. glucose infusions, i.e., no significant differences were detected between insulin responses, whereas glucose increments were reduced during the dark period. These results show that there is a circadian regulation of basal blood glucose and feeding-induced insulin responses, which is independent of the temporal distribution of feeding activity. (C) 1998 Elsevier Science Inc.

Background. In non-diabetic subjects, an attenuated systemic norepinephrine (NE) responsiveness may contribute to the mechanisms of action of angiotensin-converting enzyme (ACE) inhibitor treatment. We determined whether ACE inhibitor treatment influences systemic and renal haemodynamic responsiveness to exogenous NE, as well as urinary albumin excretion during NE, in microalbuminuric insulin-dependent diabetic (IDDM) patients, representing a patient category that benefits by strict blood pressure control. Methods. In seven microalbuminuric IDDM patients, systemic and renal responsiveness to NE, infused at individually determined threshold [Delta mean arterial pressure (MAP) = 0 mmHg], 20% pressor (Delta MAP = 4 mmHg) and presser (Delta MAP = 20 mmHg) doses, were compared before and after 8 weeks treatment with enalapril, 10 mg daily. Blood glucose was clamped at 5 mmol/l and insulin was infused at 30 mU/kg/h. Results. Enalapril decreased MAP (P Conclusions. Enalapril does not attenuate systemic and renal vascular responsiveness to exogenous NE in microalbuminuric IDDM despite adequate inhibition of the renin-angiotensin-aldosterone system. These findings suggest that the effect of NE on vasoconstriction is not counteracted effectively by ACE inhibition treatment alone.

Human plasma contains two lipid transfer proteins involved in the remodelling of plasma lipoproteins: cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP). CETP mediates the transfer/exchange of cholesterylesters, triglycerides and phospholipids between high-density lipoproteins (HDL) and chylomicron (remnants), very low-density lipoproteins (VLDL) and low density lipoproteins (LDL). The physiological function of PLTP is unknown. It is able to transfer phospholipids (but not neutral lipids) between Lipoproteins and to modulate HDL particle size in vitro. The effects of acute endogenous hyperinsulinaemia on plasma CETP and PLTP activity, as well as on lipid and lipoprotein levels, were assessed in eight healthy men during a 3-h hyperglycaemic clamp. Another group of seven men received an infusion of an equal volume of saline in order to detect possible dilution effects or effects on lipoprotein changes over time (control group). Plasma cholesterol and triglyceride concentrations fell during the clamp and the decreases were significantly different from the minor changes during saline infusion in the control group (p

Risks associated with hypertension Hypertension is a risk factor for cardiovascular and possibly renal organ damage. Microalbuminuria is a newly recognized cardiovascular and renal risk factor in diabetic and non-diabetic subjects. The prevalence of microalbuminuria is enhanced in hypertensive subjects, in particular in those with blood pressure characteristics that are associated with enhanced cardiovascular risk, such as salt-sensitivity and an abnormal diurnal blood pressure rhythm. Need for further trials Although microalbuminuria is more prevalent in hypertensives and is shown to be a strong and independent risk factor, the relation between microalbuminuria and hypertensive complications is unknown. Even more intriguing is the finding of elevated levels of microalbuminuria in normotensive children with one or two parents with hypertension. This suggests that microalbuminuria is linked to the pathogenesis of hypertension. However, the role and the cause(s) of microalbuminuria are uncertain. Microalbuminuria seems to link renal and cardiovascular organ damage. Microalbuminuria might be the consequence of (renal) organ damage induced by hypertension. Alternatively, microalbuminuria might be an independent marker of some process that occurs separately from diabetes, hypertension or dyslipidemia. Endothelial dysfunction has been suggested to underlie renal and/or cardiovascular organ damage in these diseases. More knowledge should be obtained on the cause and the natural course of microalbuminuria. Conclusion Microalbuminuria possibly identifies at an early stage hypertensive patients with an enhanced risk of developing the well-known renal and cardiovascular hypertensive complications. For the patients at particular risk therapeutic measures then can be developed. If microalbuminuria identifies a specific underlying pathogenetic mechanism, these measures may intervene with such a mechanism. Alternatively, if microalbuminuria identifies enhanced risk then standard antihypertensive therapy can be intensified, since such measures also lower microalbuminuria.

Objectives. Essential hypertension may be associated with abnormalities in free fatty acids (FFA) and triglyceride metabolism, which could lead to alterations in high density lipoproteins (HDL). Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from HDL towards triglyceride-rich lipoproteins. We compared baseline plasma lipids, HDL lipids, plasma LCAT and CETP activity as well as the lowering Of plasma FFA and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia in patients with essential hypertension and control subjects. Setting. University Hospital, Groningen. Subjects and design. Eight patients with essential hypertension and eight control subjects were studied during a 3-h hyperglycaemic glucose clamp (blood glucose, 10 mmol L(-1)). Main outcome measures. Plasma insulin, FFA, triglycerides and HDL lipids, plasma LCAT and CETP. Results. Baseline plasma FFA, total cholesterol and HDL cholesterol were not different between the groups, but plasma triglycerides tended to be higher in the hypertensive patients (P Conclusion. The action of insulin on FFA metabolism is impaired which is likely to contribute to higher plasma triglycerides in essential hypertension. In turn, higher triglycerides influence the HDL lipid composition, either directly or via an effect on the plasma LCAT/CETP ratio.

We studied the association between insulin and glucose levels and bone mineral density (BMD) in a population based study of 5931 elderly men and women, Serum insulin was measured 2 h after a nonfasting oral glucose load in subjects not using antidiabetes medication, BMD was measured by dual-energy X-ray absorptiometry in the lumbar spine and the proximal femur, In addition, the participants were asked about fractures in the preceding 5 years. Higher bone mass was associated with higher glucose and postload insulin levels at all sites, as well as with increased waist/hip ratio and body mass index, In men, the mean age-adjusted BRID at the lumbar spine (in mg/cm(2)) increased 4.64 per mmol/L serum glucose (95% CI 1.46-7.82) and 0.35 per mU/L postload insulin (0.17-0.53). In women, these values were 6.88 (4.37-9.39) for glucose and 0.25 (0.11-0.39) for insulin (for all analyses: p

OBJECTIVES - To determine the long-term effects of an LPD on albuminuria and renal hemodynamics in IDDM patients without nephropathy. RESEARCH DESIGN AND METHODS - We selected 31 patients with overnight albuminuria between 10 and 200 g/min and without hypertension from a referral-based diabetic clinic. One participant dropped out. A 2-yr randomized prospective study was conducted on 14 patients assigned to an LPD (0.6 g - kg-1 . day-1) and 16 patients assigned to continue their UPD. Protein intake was assessed by using urinary urea excretion. Albuminuria (three overnight collections) was measured at baseline and on seven occasions thereafter. GFR and ERPF were measured annually using [I-125]iothalamate and [I-131]hippuran, respectively. RESULTS - In the LPD group, protein intake decreased from 1.05 +/- 0.32 to 0.79 +/- 0.16 g . kg-1 . day-1 (P

Background No previous studies on the effect of genetic factors on the liability to disability retirement have been carried out. The main aim of this study was to investigate the contribution of genetic factors on disability retirement due to the most common medical causes, including depressive disorders. Methods The study sample consisted of 24 043 participants (49.7% women) consisting of 11 186 complete same-sex twin pairs including 3519 monozygotic (MZ) and 7667dizygotic (DZ) pairs. Information on retirement events during 1.1.1975–31.12.2004, including disability pensions (DPs) with diagnoses, was obtained from the Finnish nationwide official pension registers. Correlations in liability for MZ and DZ twins and discrete time correlated frailty model were used to investigate the genetic liability to age at disability retirement. Results The 30 year cumulative incidence of disability retirement was 20%. Under the best fitting genetic models, the heritability estimate for DPs due to any medical cause was 0.36 (95% CI 0.32–0.40), due to musculoskeletal disorders 0.37 (0.30–0.43), cardiovascular diseases 0.48 (0.39–0.57), mental disorders 0.42 (0.35–0.49) and all other reasons 0.24 (0.17–0.31). The effect of genetic factors decreased with increasing age of retirement. For DP due to depressive disorders, 28% of the variance was explained by environmental factors shared by family members (95% CI 21–36) and 58% of the variance by the age interval specific environmental factors (95% CI 44–71). Conclusions A moderate genetic contribution to the variation of disability retirement due to any medical cause was found. The genetic effects appeared to be stronger at younger ages of disability retirement suggesting the increasing influence of environmental factors not shared with family members with increasing age. Familial aggregation in DPs due to depressive disorders was best explained by the common environmental factors and genetic factors were not needed to account for the pattern of familial aggregation. Public Library of Science

Glucose toxicity (i.e., glucose-induced reduction in insulin secretion and action) may be mediated by an increased flux through the hexosamine-phosphate pathway. Glucosamine (GlcN) is widely used to accelerate the hexosamine pathway flux, independently of glucose. We tested the hypothesis that GlcN can affect insulin secretion and/or action in humans. In 10 healthy subjects, we sequentially performed an intravenous glucose (plus [2-3H]glucose) tolerance test (IVGTT) and a euglycemic insulin clamp during either a saline infusion or a low (1.6 micromol x min(-1) x kg(-1)) or high (5 micromol x min(-1) x kg(-1) [n = 5]) GlcN infusion. Beta-cell secretion, insulin (SI*-IVGTT), and glucose (SG*) action on glucose utilization during the IVGTT were measured according to minimal models of insulin secretion and action. Infusion of GlcN did not affect readily releasable insulin levels, glucose-stimulated insulin secretion (GSIS), or the time constant of secretion, but it increased both the glucose threshold of GSIS (delta approximately 0.5-0.8 mmol/l, P < 0.03-0.01) and plasma fasting glucose levels (delta approximately 0.3-0.5 mmol/l, P < 0.05-0.02). GlcN did not change glucose utilization or intracellular metabolism (glucose oxidation and glucose storage were measured by indirect calorimetry) during the clamp. However, high levels of GlcN caused a decrease in SI*-IVGTT (delta approximately 30%, P < 0.02) and in SG* (delta approximately 40%, P < 0.05). Thus, in humans, acute GlcN infusion recapitulates some metabolic features of human diabetes. It remains to be determined whether acceleration of the hexosamine pathway can cause insulin resistance at euglycemia in humans.