Insulin resistance characterizes glucose uptake in skeletal muscle but not in the heart in NIDDM

Abstract

Signs or symptoms of macrovascular disease are frequently found even prior to the development of noninsulin-dependent diabetes mellitus (NIDDM) [1]. This suggests that coronary heart disease (CHD) and NIDDM share a pathophysiologic feature, which predisposes to both diseases. Classic risk factors such as serum cholesterol, age, gender, hypertension and smoking explain only a fraction of the 2±4-fold increase in cardiovascular mortality in patients with NIDDM [1,2]. Insulin resistance, usually measured by quantitating the rate of insulin-stimulated glucose uptake, qualifies as the underlying pathophysiologic abnormality for both CHD and NIDDM, since it predicts, independent of other risk factors, both disorders [3,4].The mechanisms linking insulin resistance to CHD are unclear but could involve lipid abnormalities such as an increase in the concentration of atherogenic small dense LDL particles, which accompanies insu- Diabetologia (1998) Summary Skeletal muscle insulin resistance and coronary heart disease (CHD) often precede non-insulin-dependent diabetes mellitus (NIDDM). A recent study showed the myocardium of patients with CHD to be insulin resistant, independent of blood flow. We determined whether myocardial insulin resistance is a feature of NIDDM patients with no CHD. Skeletal muscle and myocardial glucose uptake were determined in 10 patients with NIDDM and 9 ageand weight-matched normal men of similar age and body mass index men using [18 F]-2-fluoro-2-deoxy-dglucose and positron emission tomography under normoglycaemic hyperinsulinaemic conditions. Whole body glucose uptake, as determined by the euglycaemic clamp technique, was significantly lower in the patients with NIDDM (35 ± 3 mmol/kg body weight´min) than the normal subjects (45 ± 3 mmol/ kg body weight´min, p < 0.02). Insulin-stimulated femoral muscle glucose uptake was significantly lower in the patients with NIDDM (71 ± 6 mmol/kg muscle´min) than in the normal subjects (96 ± 5 mmol/ kg muscle´min, p < 0.01). Whole body glucose uptake was correlated with femoral muscle glucose uptake in the entire group (r = 0.76, p < 0.001), in patients with NIDDM and in normal subjects. Rates of insulin-stimulated myocardial glucose uptake were comparable between the patients with NIDDM (814 ± 76 mmol/kg muscle´min) and the normal subjects (731 ± 63 mmol/kg muscle´min, p > 0.4). Whole body or femoral muscle, and myocardial glucose uptake were not correlated in all subjects, patients with NIDDM or normal subjects. We conclude that insulin resistance of the myocardium is not a feature of uncomplicated NIDDM. [Diabetologia (1998) 41: 555-559] Keywords Myocardium, insulin resistance, non-insulin-dependent diabetes mellitus, positron emission tomography.

Independent Association of Type 2 Diabetes and Coronary Artery Disease With Myocardial Insulin Resistance

“…The impairment of insulin-mediated myocardial glucose disposal reported by these authors in patients with type 2 diabetes ranges between 22 and 39%. Utriainen et al (13), conversely, found comparable rates of MGU in patients with type 2 diabetes and healthy control subjects under conditions of supraphysiological insulinization (200 mU ⅐ min Ϫ1 ⅐ m Ϫ2 insulin clamp) and after an overnight insulin infusion in the patients with diabetes alone. Although we cannot exclude that pharmacological insulin stimulation might overcome the defect observed in our patients, the present study clearly demonstrates that cardiac glucose uptake in response to physiological hyperinsulinemia is defective in type 2 diabetes.…”

“…Choice of the arm muscle instead of the leg, as used by other authors (7,11,13), was uniquely based on the advantage that this muscle lies within the same field of view as the myocardium and can be scanned simultaneously. Data analysis.…”

“…In a subsequent publication (12), the same authors were unable to confirm their observation, the apparent contradiction being attributed to metabolic differences between study groups. More recently, Utriainen et al (13) demonstrated that under conditions of supraphysiological insulinization, there is no reduction of 18 F-fluoro-deoxyglucose (FDG) accumulation in the myocardium of patients who have type 2 diabetes and are free of CAD.…”

Mismatch between insulin-mediated glucose uptake and blood flow in the heart of patients with Type II diabetes

“…Previous evidence also indicates that myocardial insulin resistance might be overcome by raising hyperinsulinaemia to supraphysiological concentrations in patients with uncomplicated Type II diabetes [18]. Although coronary artery disease (CAD) can be associated with myocardial insulin resistance [11] and sub-clinical CAD cannot be completely excluded in our patients, our inclusion criteria rule against this possibility; nevertheless, sub-clinical cardiovascular disease has not been related with myocardial insulin resistance.…”

Myocardial insulin resistance does not always parallel skeletal muscle and whole body insulin resistance: A mini review&lt;br&gt;—Myocardial Insulin Resistance &lt;br&gt;

“…Furthermore, Yokoyama et al also reported that MGU was similar in both hypertensive T2DM and controls despite significantly reduced SMGU and whole body glucose disposal rates in the former indicating an existence of insulin resisatnce in skeletal muscle and whole body but not in the heart in patients with T2DM and hypertension [18]. Moreover, myocardial insulin resistance was not observed when using very high insulin doses for insulin clamping (about 10 times higher than usual) while insulin resistance in the whole body and skeletal muscle was still present [19]. Consistent with this discrepancy, preserved MGU in response to insulin clamping under chronic use of sulfonylurea drugs in T2DM has been also reported [20].…”