We propose that excessive fructose intake (>50 g/d) may be one of the underlying etiologies of metabolic syndrome and type 2 diabetes. The primary sources of fructose are sugar (sucrose) and high fructose corn syrup. First, fructose intake correlates closely with the rate of diabetes worldwide. Second, unlike other sugars, the ingestion of excessive fructose induces features of metabolic syndrome in both laboratory animals and humans. Third, fructose appears to mediate the metabolic syndrome in part by raising uric acid, and there are now extensive experimental and clinical data supporting uric acid in the pathogenesis of metabolic syndrome. Fourth, environmental and genetic considerations provide a potential explanation of why certain groups might be more susceptible to developing diabetes. Finally, we discuss the counterarguments associated with the hypothesis and a potential explanation for these findings. If diabetes might result from excessive intake of fructose, then simple public health measures could have a major impact on improving the overall health of our populace.

Abstract. Diabetic nephropathy may be effectively prevented and treated by controlling glycemia and administering angiotensinconverting enzyme (ACE) inhibitors. However, strict metabolic control can be difficult, and ACE inhibitors may be poorly tolerated and only partially effective, particularly in diabetes mellitus type 2 (DM2), warranting the search for ancillary treatment. Sulodexide is a glycosaminoglycan, a new class of drug that has demonstrated nephroprotective activity in experimental investigations. The Di.N.A.S. study was a randomized, double-blind, placebo-controlled, multicenter, dose-range finding trial to evaluate the extent and duration of the hypoalbuminuric effect of oral sulodexide in diabetic patients. A total of 223 microalbuminuric and macroalbuminuric DM1 and DM2 patients with serum creatinine Յ150 mol/L and stable BP and metabolic control were recruited. They were randomly allocated to one of four groups: 50 mg/d, 100 mg/d, or 200 mg/d sulodexide daily or placebo for 4 mo (T0 to T4), with 4 mo of follow-up after drug suspension (T4 to T8). Treatment with 200 mg/d sulodexide for 4 mo significantly reduced log albumin excretion rate (logAER) from 5.25 Ϯ 0.18 at T0 to 3.98 Ϯ 0.11 at T4 (P Ͻ 0.05), which was maintained till T8 (4.11 Ϯ 0.13; P Ͻ 0.05 versus T0). Moreover, the sulodexideinduced percent reductions in AER at T4 were significantly different from the placebo value at T4 and approximately linear to dose increments (30% [confidence limits, 4 to 49%], P ϭ 0.03; 49% [30 to 63%], P ϭ 0.0001; and 74% [64 to 81%], P ϭ 0.0001 in the sulodexide 50, 100, and 200 mg/d groups, respectively. At T8, the sulodexide 200 mg/d group maintained a 62% (45 to 73%) AER significant reduction versus placebo (P ϭ 0.0001). Subanalysis by type of diabetes (DM1 versus DM2, microalbuminuric versus macroalbuminuric, or on concomitant ACE inhibitors versus not on ACE inhibitors) demonstrated similar findings. These effects were obtained without any significant variation in metabolic control and BP or serum creatinine. Very few adverse events were reported; none were serious. In conclusion, a 4-mo course of high doses of sulodexide significantly and dose-dependently improves albuminuria in DM1 and DM2 patients and micro-or macroalbuminuric patients with or without concomitant ACE inhibition. The effect on albuminuria is long-lasting and seemingly additive to the ACE inhibitory effect.Diabetes is the most common cause of end-stage renal disease (ESRD) in Western countries. In the United States, diabetes currently accounts for 44% of all new cases of ESRD (1). Despite advances in clinical care, the incidence of diabetes mellitus type 2 (DM2)-related cases of ESRD is rapidly increasing (2), and survival of DM-related ESRD patients on dialysis is markedly low (3,4).The anatomic hallmarks of diabetic nephropathy (DN) include thickening of the glomerular basement membrane (GBM) and mesangial expansion with hyalinosis both in the mesangium and capillary lumen. These lesions lead to glomerular fibrosis, which progressiv...

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Clinical and experimental data suggest that Parathormon (PTH), calcium, and phosphorus participate in left ventricular hypertrophy (LVH) and affect myocardial contractility in end-stage renal disease. Cellular calcium overload and interstitial fibrosis induced by PTH may lead to impairment of left ventricular diastolic function. Hyperphosphatemia is an independent risk of cardiovascular mortality in dialysis patients. The aim of the study was to estimate the influence of PTH and calcium-phosphorus metabolism on left ventricular structure and function in hemodialysis patients, without hypertension and antihypertensive drug therapy (SBP = 126.2 +/- 11.1 DBP = 75.8 +/- 6.5 mmHg). Echocardiographic findings in a group of 22 normotensive HD patients had been compared to 43 hypertensive HD patients. Relationships between PTH, calcium-phosphorus metabolism and echocardiography in normotensive group were then evaluated. Left ventricular mass index (LVMI) was lower in normotensive patients: 128.3 +/- 46.2 versus 165.8 +/- 46.7 (p < 0.01). The prevalence of LVH was 55% in normotensive HD patients compared to 86% in hypertensive group (p < 0.01). In normotensive group we found correlation between PTH and LVMI (r = 0.44; p < 0.05). There were also significant relationships between calcium and posterior wall thickness (r = -0.44; p < 0.05), phosphorus and LVMI (r = 0.47; p < 0.05). A significant correlation was observed between both phosphorus, calcium x phosphorus product and E/A ratio: r = -0.47 and r = -0.43, respectively (p < 0.05 both). Disturbances of calcium-phosphorus metabolism and secondary hyperparathyroidism contributes to left ventricular hypertrophy, and impaired left ventricular diastolic function in normotensive hemodialysis patients.