P 4: Association of insulin sensitivity level and atherogenic lipid profile in mild cognitive impairment

Abstract

As an early stage of cognitive decline (mild cognitive impairment (MCI)) has been linked to changes in cholesterol profiles, previous studies have suggested that decreased insulin sensitivity and dyslipidemia are consistently indicated as essential in the pathophysiology, and possibly the pathogenesis of Alzheimer disease (AD), most common form of age-related non vascular dementia. As diagnosis of MCI, the intermediate cognitive disorder between normal aging and AD, are becoming more reliable, the aim of this study was to analyze in patient with MCI the levels of (a) insulin sensitivity (IS), (b) plasma insulin (PI) and (c) lipid parameters comprising total cholesterol (Ch), low-density (LDL) and high density (HDL) Ch, triglycerides and apolipoproteins (apoAI, apoAII, apoB, Lp(a) and apoE) potentially involved the pathogenesis of the disease. We included 40 normoglycemic patients with MCI (group A; BMI: 24,43 +/−0.52 kg/m 2 , age: 69,36+/−7,31 years), and 30 matched controls (group B; BMI: 24,29+/−0,61 kg/m 2 , age: 65,38+/−6,69 years). IS was evaluated by using euglycemic hyperinsulinemic clamp method with insulin infusion rate of 1 mU/kgbw/min during 120 min and glucose infusion adjusted manually, at 5 min intervals, to maintain target euglycemia. Total glucose uptake (M value) was calculated on the basis of the amount of glucose infused during steady state period (80–120 min). PI levels were determined by radioimmunossay. Total cholesterol, HDL-Ch, and triglycerides levels were determined by using enzymatic method, and LDL-Ch was calculated using the formula of Friedewald. Apolipoproteins ApoAI, ApoAII, Lp(a), ApoB and ApoE were determined by using nephelometry method. We found that total glucose uptake was significantly lower in group A vs group B (M value; A: 7,51 +/−0,57; B:8,53 +/−0,45 mg/min/kg, p<0.01). In addition, basal PI levels were higher in group A vs group B (A: 11,37+/−1,35; B:7,39+/−0,70 mU/l, p<0.01). Moreover, the levels of total Ch and LDL-Ch were significantly higher in group A vs group B (total-Ch; A:6,34 +/−0,26; B:5,38 +/−0,35; LDL-Ch: A: 4,28 +/−0,33; B:3,19 +/−0,22 mmol/l, p<0.01). The HDL-Ch levels were significantly lower in group A vs B (A:1,34 +/−0,11; B: 1,54 +/−0,14 mmol/l, p<0.01). Simultaneously, the levels of ApoAI were significantly lower in group A vs B (A:1,69+/−0,12; B: 2,06+/−0,43 g/l, p<0.01). The levels of triglycerides and other apolipoproteins, ApoAII, ApoB, Lp(a) and ApoE, did not differ significantly between the groups. Our results have demonstrated that the presence of MCI in patients was associated with decreased IS and increases in peripheral insulin levels. Moreover, our results has been suggested overlap in patogenic influence of factors like insulin resistance and abnormal cholesterol metabolism, especially the increases in LDL-Ch, decreases in HDL-Ch and ApoAI levels in cognitive decline, which emphasise that appropriate changes to diets and lifestyles will likely reduce MCI risk, and also improve the prognosis for people already suffering from conditions like insulin resistance and dyslipidemia.