Reduction in Global Myocardial Glucose Metabolism in Subjects With 1-Hour Postload Hyperglycemia and Impaired Glucose Tolerance

Abstract

Impaired insulin-stimulated myocardial glucose uptake has occurred in patients with type 2 diabetes with or without coronary artery disease. Whether cardiac insulin resistance is present remains uncertain in subjects at risk for type 2 diabetes, such as individuals with impaired glucose tolerance (IGT) or those with normal glucose tolerance (NGT) and 1-h postload glucose ‡155 mg/dL during an oral glucose tolerance test (NGT 1-h high). This issue was examined in this study. RESEARCH DESIGN AND METHODS The myocardial metabolic rate of glucose (MRGlu) was measured by using dynamic 18 F-fluorodeoxyglucose positron emission tomography combined with a euglycemichyperinsulinemic clamp in 30 volunteers without coronary artery disease. Three groups were studied: 1) those with 1-h postload glucose <155 mg/dL (NGT 1-h low) (n 5 10), 2) those with NGT 1-h high (n 5 10), 3) and those with IGT (n 5 10). RESULTS After adjusting for age, sex, and BMI, both subjects with NGT 1-h high (23.7 6 6.4 mmol/min/100 mg; P 5 0.024) and those with IGT (16.4 6 6.0 mmol/min/ 100 mg; P < 0.0001) exhibited a significant reduction in global myocardial MRGlu; this value was 32.8 6 9.7 mmol/min/100 mg in subjects with NGT 1-h low. Univariate correlations showed that MRGlu was positively correlated with insulin-stimulated whole-body glucose disposal (r 5 0.441; P 5 0.019) and negatively correlated with 1-h (r 5 20.422; P 5 0.025) and 2-h (r 5 20.374; P 5 0.05) postload glucose levels, but not with fasting glucose. CONCLUSIONS This study shows that myocardial insulin resistance is an early defect that is already detectable in individuals with dysglycemic conditions associated with an increased risk of type 2 diabetes, such as IGT and NGT 1-h high.

Nonalcoholic fatty liver disease is associated with a decreased myocardial mechano‐energetic efficiency

“…The mechanisms underlying the relationship between NAFLD and a higher myocardial oxygen consumption and a compromised ability of the LV to convert energy into stroke work have not been characterized yet. Insulin resistance is a main feature of NAFLD, and it has been found to affect myocardial metabolism [27,29,30,34] In normal conditions, 60-70% of myocardial energy is produced by fatty acid oxidation, whilst only 30-40% of energy is derived by glucose-pyruvate oxidation. There is evidence that insulin-resistant individuals have an increased oxidation of fatty acids paralleled by a decrease in glucose uptake and metabolic utilization, which results in a higher oxygen consumption and an impaired cardiac mechanical efficiency [27,29,30,34,44,45].…”

“…Insulin resistance is a main feature of NAFLD, and it has been found to affect myocardial metabolism [27,29,30,34] In normal conditions, 60-70% of myocardial energy is produced by fatty acid oxidation, whilst only 30-40% of energy is derived by glucose-pyruvate oxidation. There is evidence that insulin-resistant individuals have an increased oxidation of fatty acids paralleled by a decrease in glucose uptake and metabolic utilization, which results in a higher oxygen consumption and an impaired cardiac mechanical efficiency [27,29,30,34,44,45]. Recently, Mancusi et al have reported an association between a higher degree of insulin resistance estimated by HOMA-IR and a reduced MEEi [30].…”

“…Moreover, we have not directly assessed myocardial insulin sensitivity. However, prior studies have demonstrated that a reduction in insulin stimulated myocardial glucose metabolism is paralleled by a decrease in wholebody insulin sensitivity and closely related to hepatic fat content [34,54]. Additionally, the lack of data regarding circulating FFAs concentrations and levels of other proinflammatory molecules such IL-6, TNF-a, known to be associated with NAFLD and CVD [15], precludes us to investigate their role in mediating the effect of NALFD on myocardial energetic disarrangement.…”

“…Study population comprises 699 nondiabetic subjects participating in the CATAnzaro MEtabolic RIsk factors (CATAMERI) study, an ongoing observational study enrolling adult Caucasian subjects whose design has been previously described [32‐35]. All participants were consecutively recruited at the Department of Medical and Surgical Sciences of the University 'Magna Graecia' of Catanzaro.…”

<p>The Oral Glucose Tolerance Test: 100 Years Later</p>

“…A series of epidemiologic analyses from the CATAnzaro Metabolic RIsk factors (CATAMERI) study provided mechanistic insights into the association of 1-h PG with various cardiovascular risk factors. This cohort has demonstrated an association between an elevated 1-h PG in individuals with NGT and subclinical target organ damage such as carotid atherosclerosis, 162 cardiac insulin resistance, 163 fatty liver, 164,165 and impaired kidney function. 166 Similar observations were also noted in other cohort studies.…”