The multi-faceted outcomes of conjunct diabetes and cardiovascular familial history in type 2 diabetes

BACKGROUND: Familial history of early-onset CHD (EOCHD) is a major risk factor for CHD. Familial diabetes history (FDH) impacts β-cell function. Some transmissible, accretional gradient of CHD risk may exist when diabetes and EOCHD familial histories combine. We investigated whether the impact of such combination is neutral, additive, or potentiating in T2DM descendants, as regards cardiometabolic phenotype, glucose homeostasis and micro-/macroangiopathies. METHODS: Cross-sectional retrospective cohort study of 796 T2DM divided according to presence (Diab[+]) or absence (Diab[−]) of 1st-degree diabetes familial history and/or EOCHD (CVD(+) and (−)). Four subgroups: (i) [Diab(−)CVD(−)] (n=355); (ii) [Diab(+)CVD(−)] (n=338); (iii) [Diab(−)CVD(+)] (n=47); and (iv) [Diab(+)CVD(+)] (n=56). RESULTS: No interaction on subgroup distribution between presence of both familial histories, the combination of which translated into additive detrimental outcomes and higher rates of fat mass, sarcopenia, ₕₛCRP and retinopathy. FDH(+) had lower insulinemia, insulin secretion, hyperbolic product, and accelerated hyperbolic product loss. An EOCHD family history affected neither insulin secretion nor sensitivity. There were significant differences regarding macroangiopathy/CAD, more prevalent in [Diab(−)CVD(+)] and [Diab(+)CVD(+)]. Among CVD(+), the highest macroangiopathy prevalence was observed in [Diab(−)CVD(+)], who had 66% macroangiopathy, and 57% CAD, rates higher (absolute-relative) by 23%–53% (overall) and 21%–58% (CAD) than [Diab(+)CVD(+)], who inherited the direst cardiometabolic familial history (p 0.0288 and 0.0310). CONCLUSIONS: A parental history for diabetes markedly affects residual insulin secretion and secretory loss rate in T2DM offspring without worsening insulin resistance. It paradoxically translated into lower macroangiopathy with concurrent familial EOCHD. Conjunct diabetes and CV familial histories generate multi-faceted vascular outcomes in offspring, including lesser macroangiopathy/CAD.