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Family histories of diabetes, early-onset CHD increase vascular risk in diabetes
Adults with diabetes and a first-degree family history of diabetes and early-onset coronary heart disease had increased microvascular or macrovascular risks, respectively, according to data published in the Journal of Diabetes.
“This study shows that two common [family histories], although inherited independently of each other, modulate the phenotype of offspring with diabetes to such an extent that they deserve separate characterization,” Michel Hermans, MD, PhD, professor and chief of clinic in the division of endocrinology and nutrition at Cliniques-Universitaires St-Luc and Institut de Recherche Expérimentale et Clinique at Université Catholique de Louvain, Brussels, and colleagues wrote. “Our factorial approach makes it possible to distinguish the specific phenotypes conveyed by these parent histories in isolation or in combination. ... Our observations point out a likely contribution of hyperinsulinemia, dysfunctional HDLs and [lipoprotein(a)] as emerging mediators of inherited macrovascular risk.”
In the cross-sectional study, researchers analyzed archived medical records and parent histories of 1,098 adults with type 2 diabetes who attended the diabetes clinic at St-Luc academic hospital in Brussels. Half of patients (n = 550) had a self-reported first-degree family history of diabetes, and 13% (n = 145) had a first-degree family history of early-onset CHD.
Compared with those without a family history of diabetes, patients with first-degree relatives with diabetes were younger when diagnosed with diabetes by an average of 5 years and had a moderate increase of 4% in family history of early-onset CHD. Family history of diabetes was also associated with statistically significantly higher BMI and fat mass, lower skeletal muscle mass, lower insulin sensitivity and beta-cell function, worse glycemic control (0.23% HbA1c), increased high-sensitivity C-reactive protein and higher total and LDL cholesterol. They also had significantly increased rates of retinopathy and polyneuropathy, but the presence of macrovascular complications was similar to that of patients without a family history of diabetes.
Compared with those without a family history of early-onset CHD, patients with a family history were older at diabetes diagnosis by a mean of 9 years. These patients also had statistically significantly higher fat mass, lower skeletal muscle mass, greater insulinemia and an increased metabolic syndrome score. They were prescribed fibrates significantly more often than patients without a family history of early-onset CHD. Although their total and LDL cholesterol levels were similar to those of patients without a family history, those with a family history had higher lipoprotein(a) (median lipoprotein(a) increased by 19 nmol/L, or 83%). Patients with and without a family history of early-onset CHD did not differ in microangiopathies, but those with a family history had a significantly higher prevalence of all-cause macroangiopathy (27% absolute; 82% relative), coronary artery disease (26% absolute; 218% relative), transient ischemic attack/stroke (6% absolute; 67% relative) and peripheral artery disease (5% absolute; 56% relative).
The researchers created four subgroups of patients: those with a family history of both diabetes and early-onset CHD, those with a family history of diabetes but not early-onset CHD, those without a family history of diabetes but with a family history of early-onset CHD, and those without a family history of either condition.
Researchers found statistically significant differences between patients with a family history of both conditions vs. those with no family history of either condition. Those in the former group had an earlier age of diabetes onset (6 years) and significantly increased prevalence of diabetic retinopathy (12% absolute; 63% relative), greater frequency of overall macroangiopathy (18% absolute; 50% relative) and CAD (19% absolute; 76% relative), higher fat mass, lower skeletal muscle mass and higher pretreatment triglycerides level (45%).
The researchers wrote that they had expected the higher cardiovascular risk found among patients with a family history of diabetes would be magnified among those with a family history of both diabetes and early-onset CHD. However, patients with a family history of both were less likely to have macroangiopathy than those patients with only a family history of early-onset CHD.
“This is seemingly counterintuitive when one assumes that a diabetic parental inheritance predisposes to increased macrovascular risk,” the researchers wrote. “Thus, the attenuating influence of diabetes family history on macroangiopathic risk imparted by an early-onset CHD parental history was unexpected, and one needs to consider other underlying pathophysiological factors.” – by Tina DiMarcantonio-Brown
Disclosures: The authors report no relevant financial disclosures.