High prevalence of risk factors for cardiovascular disease in parents of IDDM patients with albuminuria

Abstract

In insulin-dependent diabetic (IDDM) patients survival is significantly affected by the development of nephropathy which leads to renal failure and increased cardiovascular mortality [1].Raised albumin excretion rate (AER) per se is strongly related to early cardiovascular morbidity and mortality both in insulin-dependent and non-insulin-dependent (NIDDM) diabetic patients [2,3]. Moreover IDDM patients with microalbuminuria, a Diabetologia (1997) Summary Life expectancy is shorter in the subset of insulin-dependent diabetic (IDDM) patients who are susceptible to kidney disease. Familial factors may be important. In this study the prevalence of cardiovascular disease mortality and morbidity and of risk factors for cardiovascular disease was compared in the parents of 31 IDDM patients with elevated albumin excretion rate (AER > 45 m g/min; group A) with that of parents of 31 insulin-dependent diabetic patients with normoalbuminuria (AER < 20 m g/min; group B). The two diabetic patient groups were matched for age and duration of disease. Information on deceased parents was obtained from death certificates and clinical records and morbidity for cardiovascular disease was ascertained using the World Health Organization questionnaire and Minnesota coded ECG. Hyperlipidaemia was defined as serum cholesterol higher than 6 mmol/l and/or plasma triglycerides higher than 2.3 mmol/l and/or lipid lowering therapy; arterial hypertension as systolic blood pressure higher than 140 mmHg and/or diastolic blood pressure higher than 90 mmHg and/or antihypertensive treatment. The percentage of dead parents was similar in the two groups (26 vs 20 % for parents of group A vs group B, respectively), but the parents of the diabetic patients with elevated AER had died at a younger age (58 ± 10 vs 70 ± 14 years; p < 0.05). Parents of diabetic patients with nephropathy had a more than three times greater frequency of combined mortality and morbidity for cardiovascular disease than that of the parents of diabetic patients without nephropathy (26 vs 8 %; odds ratio 3.96, 95 % CI 1.3 to 12.2; p < 0.02). Living parents of group A had a higher prevalence of arterial hypertension (42 vs 14 % p < 0.01) and hyperlipidaemia (49 vs 26 % p < 0.05) as well as higher levels of lipoprotein (a) [median (range) 27.2 (1-107) vs 15.6 (0.2-98) mg/dl; p < 0.05]. They also had reduced insulin sensitivity [insulin tolerance test: median (range) K itt index: 3.7 (0.7-6.2) vs 4.8 (0.7-6.7)% per min; p < 0.05]. In the families of IDDM patients with elevated AER there was a higher frequency of risk factors for cardiovascular disease as well as a predisposition to cardiovascular disease events. This may help explain, in part, the high prevalence of cardiovascular disease mortality and morbidity in those IDDM patients who develop nephropathy.

Increased plasma adiponectin concentrations are associated with microangiopathy in type 1 diabetic subjects

“…This reflects their association with insulin resistance in type 1 diabetic patients and in non-diabetic control subjects, and is consistent with many other observations [19]. As insulin resistance has been shown to be related to diabetic retinopathy and nephropathy in prospective [20,21] and family-based studies [6,7], we expected patients with severe retinopathy and incident microalbuminuria to have relatively lower levels of adiponectin. Furthermore, recent reports suggest a role for low-grade inflammation in diabetic microangiopathy, particularly that caused by IL-6 [22,23].…”

“…Furthermore, parental insulin resistance is associated with diabetic nephropathy, which strongly suggests that insulin resistance plays a role in the development of microangiopathy in type 1 diabetes patients [6,7].…”

Factors associated with progression to macroalbuminuria in microalbuminuric Type 1 diabetic patients: the EURODIAB Prospective Complications Study

“…Insulin resistance is a feature of Type 1 diabetic patients with microalbuminuria, and this contributes to the increased risk of cardiovascular disease in these patients [34,35]. Notably, in the univariate analysis of this study, both fasting triglyceride and vWF plasma levels, both of which are associated with the insulin resistance syndrome, were significantly higher in patients progressing to overt albuminuria.…”

A Haplotype at the Adiponectin Locus Is Associated With Obesity and Other Features of the Insulin Resistance Syndrome

“…Systolic and diastolic (disappearance of Korotkoff sound, phase V) blood pressure were measured in the sitting position with an appropriately sized cuff after a 5-min rest. Plasma glucose (mmol/l), serum insulin (pmol/l), and lipid profile (total serum cholesterol, HDL cholesterol, serum triglycerides) were measured using commercially available enzymatic kits as previously described (23). The insulin resistance index HOMA IR (homeostasis model assessment) was calculated as fasting serum insulin (pmol/l) ϫ fasting plasma glucose (mmol/l)/135 (24).…”